Ferroptosis-centered Disease Response Information
General Information of the Disease (ID: DIS00027)
Name |
Colon cancer
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ICD |
ICD-11: 2B90
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Full List of Target(s) of This Ferroptosis-centered Disease
Ferroptosis suppressor protein 1 (AIFM2)
In total 2 item(s) under this target | ||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [1] | |||
Target for Ferroptosis | Suppressor | |||
Responsed Disease | Colon carcinoma [ICD-11: 2B90] | |||
Responsed Drug | NCS207895 | Investigative | ||
Responsed Regulator | Protein Mdm4 (MDM4) | Driver | ||
Pathway Response | Fatty acid metabolism | hsa01212 | ||
Ferroptosis | hsa04216 | |||
Cell Process | Cell ferroptosis | |||
In Vitro Model | HCT 116 cells | Colon carcinoma | Homo sapiens | CVCL_0291 |
NCI-H1299 cells | Lung large cell carcinoma | Homo sapiens | CVCL_0060 | |
SK-HEP-1 cells | Liver and intrahepatic bile duct epithelial neoplasm | Homo sapiens | CVCL_0525 | |
HT-1080 cells | Fibrosarcoma | Homo sapiens | CVCL_0317 | |
Response regulation | Inhibition of MDM2 (Nutlin-3) or MDMX (NCS207895) leads to increased levels of FSP1 protein and a consequent increase in the levels of coenzyme Q10, an endogenous lipophilic antioxidant. This suggests that MDM2 and MDMX normally prevent cells from mounting an adequate defense against lipid peroxidation and thereby promote ferroptosis in Colon carcinoma. | |||
Experiment 2 Reporting the Ferroptosis-centered Disease Response by This Target | [1] | |||
Target for Ferroptosis | Suppressor | |||
Responsed Disease | Colon carcinoma [ICD-11: 2B90] | |||
Responsed Drug | Nutlin-3 | Investigative | ||
Responsed Regulator | E3 ubiquitin-protein ligase Mdm2 (MDM2) | Driver | ||
Pathway Response | Fatty acid metabolism | hsa01212 | ||
Ferroptosis | hsa04216 | |||
Cell Process | Cell ferroptosis | |||
In Vitro Model | HCT 116 cells | Colon carcinoma | Homo sapiens | CVCL_0291 |
NCI-H1299 cells | Lung large cell carcinoma | Homo sapiens | CVCL_0060 | |
SK-HEP-1 cells | Liver and intrahepatic bile duct epithelial neoplasm | Homo sapiens | CVCL_0525 | |
HT-1080 cells | Fibrosarcoma | Homo sapiens | CVCL_0317 | |
Response regulation | Inhibition of MDM2 (Nutlin-3) or MDMX (NCS207895) leads to increased levels of FSP1 protein and a consequent increase in the levels of coenzyme Q10, an endogenous lipophilic antioxidant. This suggests that MDM2 and MDMX normally prevent cells from mounting an adequate defense against lipid peroxidation and thereby promote ferroptosis in Colon carcinoma. | |||
Cystine/glutamate transporter (SLC7A11)
In total 3 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [2] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Colon carcinoma [ICD-11: 2B90] | ||||
Responsed Drug | Sulfasalazine | Investigative | |||
Responsed Regulator | 5'-AMP-activated protein kinase catalytic subunit alpha-2 (PRKAA2) | Driver | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
AMPK signaling pathway | hsa04152 | ||||
Autophagy | hsa04140 | ||||
Cell Process | Cell ferroptosis | ||||
Cell autophagy | |||||
In Vitro Model | HCT 116 cells | Colon carcinoma | Homo sapiens | CVCL_0291 | |
PANC-1 cells | Pancreatic ductal adenocarcinoma | Homo sapiens | CVCL_0480 | ||
HT-1080 cells | Fibrosarcoma | Homo sapiens | CVCL_0317 | ||
Calu-1 cells | Lung squamous cell carcinoma | Homo sapiens | CVCL_0608 | ||
HeLa cells | Endocervical adenocarcinoma | Homo sapiens | CVCL_0030 | ||
HEK-293T cells | Normal | Homo sapiens | CVCL_0063 | ||
In Vivo Model |
To generate murine subcutaneous tumors, 5 x 106 HCT116, CX-1, or HT1080 cells in 100 ul phosphate buffered saline (PBS; Thermo Fisher Scientific, AM9625) were injected subcutaneously right of the dorsal midline in athymic nude immunodeficient mice (six- to eight-week-old, female). To generate orthotopic tumors, 1 x 106 KPC cells in 10 ul PBS were surgically implanted into the pancreases of immunocompetent C57BL/6J mice (six- to eight-week-old, female).
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Response regulation | BECN1 plays a novel role in lipid peroxidation that could be exploited to improve anticancer therapy by the induction of ferroptosis. Mechanistically, phosphorylation of BECN1 at Ser90/93/96 by PRKAA/ AMPK contributes to the formation of a BECN1-SLC7A11 complex and system Xc-inhibition. Knockdown of BECN1 by shRNA inhibits ferroptosis induced by system X-c- inhibitors (e.g., erastin, sulfasalazine, and sorafenib) in Colon carcinoma. | ||||
Experiment 2 Reporting the Ferroptosis-centered Disease Response by This Target | [2] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Colon carcinoma [ICD-11: 2B90] | ||||
Responsed Drug | Sulfasalazine | Investigative | |||
Responsed Regulator | 5'-AMP-activated protein kinase catalytic subunit alpha-2 (PRKAA2) | Driver | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
AMPK signaling pathway | hsa04152 | ||||
Autophagy | hsa04140 | ||||
Cell Process | Cell ferroptosis | ||||
Cell autophagy | |||||
In Vitro Model | HCT 116 cells | Colon carcinoma | Homo sapiens | CVCL_0291 | |
PANC-1 cells | Pancreatic ductal adenocarcinoma | Homo sapiens | CVCL_0480 | ||
HT-1080 cells | Fibrosarcoma | Homo sapiens | CVCL_0317 | ||
Calu-1 cells | Lung squamous cell carcinoma | Homo sapiens | CVCL_0608 | ||
HeLa cells | Endocervical adenocarcinoma | Homo sapiens | CVCL_0030 | ||
HEK-293T cells | Normal | Homo sapiens | CVCL_0063 | ||
In Vivo Model |
To generate murine subcutaneous tumors, 5 x 106 HCT116, CX-1, or HT1080 cells in 100 ul phosphate buffered saline (PBS; Thermo Fisher Scientific, AM9625) were injected subcutaneously right of the dorsal midline in athymic nude immunodeficient mice (six- to eight-week-old, female). To generate orthotopic tumors, 1 x 106 KPC cells in 10 ul PBS were surgically implanted into the pancreases of immunocompetent C57BL/6J mice (six- to eight-week-old, female).
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Response regulation | BECN1 plays a novel role in lipid peroxidation that could be exploited to improve anticancer therapy by the induction of ferroptosis. Mechanistically, phosphorylation of BECN1 at Ser90/93/96 by PRKAA/AMPK contributes to the formation of a BECN1-SLC7A11 complex and system Xc-inhibition. Knockdown of BECN1 by shRNA inhibits ferroptosis induced by system X-c- inhibitors (e.g., erastin, sulfasalazine, and sorafenib) in Colon carcinoma. | ||||
Experiment 3 Reporting the Ferroptosis-centered Disease Response by This Target | [5] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Colon cancer [ICD-11: 2B90] | ||||
Responsed Drug | Pt3R5G | Investigative | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
In Vitro Model | RKO cells | Colon carcinoma | Homo sapiens | CVCL_0504 | |
HCT 116 cells | Colon carcinoma | Homo sapiens | CVCL_0291 | ||
NCM460 cells | Normal | Homo sapiens | CVCL_0460 | ||
In Vivo Model |
Five-week-old male BALB/c-nude mice from Central Laboratory of Animal, Xi'an Jiaotong University Health Science Center were housed 4 per cage under controlled temperature (23 ± 2 ), a 12 h/12 h light/dark cycle with ad libitum access to food and water and specific pathogen-free conditions. Twelve BALB/c-nude mice were randomly divided into three groups (control, 25 mg/kg, 50 mg/kg). 1 x 106 RKO cells were subcutaneously injected into either side of the same mice dorsal flanks. After 14 days, animals then received Pt3R5G (25 mg/kg, 50 mg/kg) byintraperitoneal injectionfor 15 days. The weight of mouse and tumor nodules sizer were measured every 3 days for 29 days.
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Response regulation | Pt3R5G significantly down-regulated SLC7A11 expression and up-regulated TFR1 in RKO cells. Pt3R5G inhibits cell proliferation through inducing ferroptosis by down-regulating SLC7A11 in colon cancer. | ||||
Unspecific Target
In total 8 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [3] | ||||
Responsed Disease | Colon cancer [ICD-11: 2B90] | ||||
Responsed Drug | Albiziabioside A | Investigative | |||
Responsed Regulator | Cellular tumor antigen p53 (TP53) | Driver | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Apoptosis | hsa04210 | ||||
Cell Process | Cell ferroptosis | ||||
Cell apoptosis | |||||
In Vitro Model | MCF-7 cells | Breast carcinoma | Homo sapiens | CVCL_0031 | |
HCT 116 cells | Colon carcinoma | Homo sapiens | CVCL_0291 | ||
hBMECs (Human brain microvascular endothelial cells) | |||||
L-02 cells | Endocervical adenocarcinoma | Homo sapiens | CVCL_6926 | ||
HaCaT cells | Normal | Homo sapiens | CVCL_0038 | ||
HCT-8 cells | Ileocecal adenocarcinoma | Homo sapiens | CVCL_2478 | ||
Hep-G2 cells | Hepatoblastoma | Homo sapiens | CVCL_0027 | ||
A-549 cells | Lung adenocarcinoma | Homo sapiens | CVCL_0023 | ||
CCD-841CoN cells | Normal | Homo sapiens | CVCL_2871 | ||
BEAS-2B cells | Normal | Homo sapiens | CVCL_0168 | ||
BEL-7402 cells | Endocervical adenocarcinoma | Homo sapiens | CVCL_5492 | ||
In Vivo Model |
A total of 1 x 107 HCT116 cells were subcutaneously inoculated into the right flank of BALB/c mice. When tumor reached 70-100 mm3 (10 days after implant), mice were divided into five groups of eight animals at random. The groups with D13 were administered intravenously 20 mg/kg and 10 mg/kg. The positive control group was treated with AlbA(20 mg/kg and 10 mg/kg) through intravenous injection. The negative control group received 0.9% normal saline through intravenous injection.
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Response regulation | The study synthesized a series of Albiziabioside A derivatives and evaluated the antitumor activity both in vitro and in vivo. Compound D13 could induce apoptosis and ferroptosis through the mitochondrial pathway as a p53 activator. In addition, compound D13 significantly suppressed tumorigenesis without inducing toxicity in normal organs in vivo. The antitumor efficacy of D13 was further verified in colon cancer xenograft mouse models. | ||||
Experiment 2 Reporting the Ferroptosis-centered Disease Response by This Target | [4] | ||||
Responsed Disease | Colon cancer [ICD-11: 2B90] | ||||
Responsed Drug | Ginkgo biflavones | Investigative | |||
Responsed Regulator | E3 ubiquitin-protein ligase Mdm2 (MDM2) | Suppressor | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | HCT 116 cells | Colon carcinoma | Homo sapiens | CVCL_0291 | |
HT29 cells | Colon cancer | Mus musculus | CVCL_A8EZ | ||
RKO cells | Colon carcinoma | Homo sapiens | CVCL_0504 | ||
LoVo cells | Colon adenocarcinoma | Homo sapiens | CVCL_0399 | ||
SW620 cells | Colon adenocarcinoma | Homo sapiens | CVCL_0547 | ||
In Vivo Model |
HCT-116 cells (5 x 106) were injected into the flanks of 6-week-old male BALB/c nude mice to generate xenografts. The mice were randomly divided into four groups (n = 7 per group), and treatment was started at 96 h postinjection. The mice received an intraperitoneal injection (i.p.) of 0.9% saline solution containing 5% dimethyl sulfoxide (DMSO) (vehicle for blank control) and ginkgetin (10 mg/kg) once a day, respectively, and 5-FU (30 mg/kg) was used as the positive control (i.p., once every 3 days, alternately).
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Response regulation | Ginkgo biflavones can increase the expression level of p53 by inhibiting the expression of MDM2 protein and induce cell death independent of p53 transcriptional activity in vitro. And we provide evidence that ginkgetin strengthened the antitumor effect of fluorouracil (5-FU) in the HCT-116 colon cancer xenograft model. | ||||
Experiment 3 Reporting the Ferroptosis-centered Disease Response by This Target | [4] | ||||
Responsed Disease | Colon cancer [ICD-11: 2B90] | ||||
Responsed Drug | Ginkgo biflavones | Investigative | |||
Responsed Regulator | Cellular tumor antigen p53 (TP53) | Driver | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | HCT 116 cells | Colon carcinoma | Homo sapiens | CVCL_0291 | |
HT29 cells | Colon cancer | Mus musculus | CVCL_A8EZ | ||
RKO cells | Colon carcinoma | Homo sapiens | CVCL_0504 | ||
LoVo cells | Colon adenocarcinoma | Homo sapiens | CVCL_0399 | ||
SW620 cells | Colon adenocarcinoma | Homo sapiens | CVCL_0547 | ||
In Vivo Model |
HCT-116 cells (5 x 106) were injected into the flanks of 6-week-old male BALB/c nude mice to generate xenografts. The mice were randomly divided into four groups (n = 7 per group), and treatment was started at 96 h postinjection. The mice received an intraperitoneal injection (i.p.) of 0.9% saline solution containing 5% dimethyl sulfoxide (DMSO) (vehicle for blank control) and ginkgetin (10 mg/kg) once a day, respectively, and 5-FU (30 mg/kg) was used as the positive control (i.p., once every 3 days, alternately).
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Response regulation | Ginkgo biflavones can increase the expression level of p53 by inhibiting the expression of MDM2 protein and induce cell death independent of p53 transcriptional activity in vitro. And we provide evidence that ginkgetin strengthened the antitumor effect of fluorouracil (5-FU) in the HCT-116 colon cancer xenograft model. | ||||
Experiment 4 Reporting the Ferroptosis-centered Disease Response by This Target | [9] | ||||
Responsed Disease | Colon cancer [ICD-11: 2B90] | ||||
Responsed Drug | Soyauxinium chloride | Investigative | |||
Pathway Response | Apoptosis | hsa04210 | |||
Ferroptosis | hsa04216 | ||||
Necroptosis | hsa04217 | ||||
Cell Process | Cell ferroptosis | ||||
Cell apoptosis | |||||
Cell necroptosis | |||||
In Vitro Model | HCT 116 cells | Colon carcinoma | Homo sapiens | CVCL_0291 | |
CC531 cells | Colon adenocarcinoma | Rattus norvegicus | CVCL_0206 | ||
Response regulation | The prominent cytotoxic potential of soyauxinium chloride (SCHL) on a panel of 18 human and animal cancer cell lines, including MDR phenotypes. This investigated indoloquinazoline alkaloid induced apoptosis in CCRF-CEM cellsviacaspases activation, MMP alteration and increase of ROS production, and caused ferroptosis and necroptosis in colon cancer. | ||||
Experiment 5 Reporting the Ferroptosis-centered Disease Response by This Target | [10] | ||||
Responsed Disease | Colon cancer [ICD-11: 2B90] | ||||
Responsed Regulator | Neutral ceramidase (ASAH2) | Suppressor | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | CT26 cells | Colon adenocarcinoma | Mus musculus | CVCL_7254 | |
4T1 cells | Mammary carcinoma | Mus musculus | CVCL_0125 | ||
In Vivo Model |
BALB/c and C57BL/6 mice were obtained from the Jackson Laboratory (Bar Harbor, ME). To establish subcutaneous tumor models, CT26 cells (2 x 105 cells/mouse) were injected into the right flanks of BALB/c mice. For experimental lung metastasis models, colon carcinoma CT26, mesothelioma AB1 (2 x 105 cells/mouse) and mammary carcinoma 4T1 (2 x 104 cells/mouse) were injected into BALB/c mice. Tumor-bearing mice were treated with vehicle PEG300 (Sigma-Aldrich) and NC06 (dissolved in PEG300), respectively, every two days for 3-5 times by Intraperitoneal injection.
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Response regulation | ASAH2 is overexpressed in MDSCs in human colon cancer patients. ASAH2 protects MDSCs from ferroptosis through destabilizing p53 protein to suppress the p53 pathway in MDSCs in the tumor microenvironment. | ||||
Experiment 6 Reporting the Ferroptosis-centered Disease Response by This Target | [11] | ||||
Responsed Disease | Colon cancer [ICD-11: 2B90] | ||||
Responsed Regulator | Cytoglobin (CYGB) | Driver | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Hippo signaling pathway | hsa04390 | ||||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
In Vitro Model | HCT 116 cells | Colon carcinoma | Homo sapiens | CVCL_0291 | |
SW620 cells | Colon adenocarcinoma | Homo sapiens | CVCL_0547 | ||
Response regulation | CYGB significantly increased the sensitivity of cancer cells to RSL3- and erastin-induced ferroptotic cell death. Collectively, a novel tumour suppressor role of CYGB through p53-YAP1 axis in regulating ferroptosis and suggested a potential therapeutic approach for colon cancer. | ||||
Experiment 7 Reporting the Ferroptosis-centered Disease Response by This Target | [10] | ||||
Responsed Disease | Colon cancer [ICD-11: 2B90] | ||||
Responsed Regulator | Cellular tumor antigen p53 (TP53) | Driver | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | CT26 cells | Colon adenocarcinoma | Mus musculus | CVCL_7254 | |
4T1 cells | Mammary carcinoma | Mus musculus | CVCL_0125 | ||
In Vivo Model |
BALB/c and C57BL/6 mice were obtained from the Jackson Laboratory (Bar Harbor, ME). To establish subcutaneous tumor models, CT26 cells (2 x 105 cells/mouse) were injected into the right flanks of BALB/c mice. For experimental lung metastasis models, colon carcinoma CT26, mesothelioma AB1 (2 x 105 cells/mouse) and mammary carcinoma 4T1 (2 x 104 cells/mouse) were injected into BALB/c mice. Tumor-bearing mice were treated with vehicle PEG300 (Sigma-Aldrich) and NC06 (dissolved in PEG300), respectively, every two days for 3-5 times by Intraperitoneal injection.
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Response regulation | ASAH2 is overexpressed in MDSCs in human colon cancer patients. ASAH2 protects MDSCs from ferroptosis through destabilizing p53 protein to suppress the p53 pathway in MDSCs in the tumor microenvironment. | ||||
Experiment 8 Reporting the Ferroptosis-centered Disease Response by This Target | [11] | ||||
Responsed Disease | Colon cancer [ICD-11: 2B90] | ||||
Responsed Regulator | Cellular tumor antigen p53 (TP53) | Driver | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Hippo signaling pathway | hsa04390 | ||||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
In Vitro Model | HCT 116 cells | Colon carcinoma | Homo sapiens | CVCL_0291 | |
SW620 cells | Colon adenocarcinoma | Homo sapiens | CVCL_0547 | ||
Response regulation | CYGB significantly increased the sensitivity of cancer cells to RSL3- and erastin-induced ferroptotic cell death. Collectively, a novel tumour suppressor role of CYGB through p53-YAP1 axis in regulating ferroptosis and suggested a potential therapeutic approach for colon cancer. | ||||
Transferrin receptor protein 1 (TFRC)
In total 1 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [5] | ||||
Target for Ferroptosis | Marker/Suppressor/Driver | ||||
Responsed Disease | Colon cancer [ICD-11: 2B90] | ||||
Responsed Drug | Pt3R5G | Investigative | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
In Vitro Model | RKO cells | Colon carcinoma | Homo sapiens | CVCL_0504 | |
HCT 116 cells | Colon carcinoma | Homo sapiens | CVCL_0291 | ||
NCM460 cells | Normal | Homo sapiens | CVCL_0460 | ||
In Vivo Model |
Five-week-old male BALB/c-nude mice from Central Laboratory of Animal, Xi'an Jiaotong University Health Science Center were housed 4 per cage under controlled temperature (23 ± 2 ), a 12 h/12 h light/dark cycle with ad libitum access to food and water and specific pathogen-free conditions. Twelve BALB/c-nude mice were randomly divided into three groups (control, 25 mg/kg, 50 mg/kg). 1 x 106 RKO cells were subcutaneously injected into either side of the same mice dorsal flanks. After 14 days, animals then received Pt3R5G (25 mg/kg, 50 mg/kg) byintraperitoneal injectionfor 15 days. The weight of mouse and tumor nodules sizer were measured every 3 days for 29 days.
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Response regulation | Pt3R5G significantly down-regulated SLC7A11 expression and up-regulated TFR1 in RKO cells. Pt3R5G inhibits cell proliferation through inducing ferroptosis by down-regulating SLC7A11 in colon cancer. | ||||
Stearoyl-CoA desaturase (SCD)
In total 2 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [6] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Colon cancer [ICD-11: 2B90] | ||||
Responsed Regulator | hsa-miR-423-5p (miRNA) | Driver | |||
Pathway Response | Wnt signaling pathway | hsa04310 | |||
Fatty acid metabolism | hsa01212 | ||||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
Cell stemness | |||||
In Vitro Model | SW480 cells | Colon adenocarcinoma | Homo sapiens | CVCL_0546 | |
HT29 cells | Colon cancer | Mus musculus | CVCL_A8EZ | ||
HEK-293T cells | Normal | Homo sapiens | CVCL_0063 | ||
In Vivo Model |
Four-week-old female nude mice were purchased from Cavens (Changzhou, China). Nude mice were randomly divided into four groups. SW480 and HT29 cells infected with sh-LINC01606, Lv-LINC01606 and control vectors were subcutaneously implanted in mice (n = 6 per group), respectively. Tumour volumes (V = length x width2/2) were measured every 3 days, and tumour weights were determined after 4 weeks.
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Response regulation | LINC01606 functions as an oncogene to facilitate tumor cell stemness, proliferation and inhibit ferroptosis and is a promising therapeutic target for colon cancer. Mechanistically, LINC01606 enhanced the expression of stearoyl-CoA desaturase 1 (SCD1), serving as a competing endogenous RNA to modulate miR-423-5p expression, subsequently activating the canonical Wnt/-catenin signaling, and transcription factor binding to IGHM enhancer 3 (TFE3) increased LINC01606 transcription after recruitment to the promoter regions of LINC01606. | ||||
Experiment 2 Reporting the Ferroptosis-centered Disease Response by This Target | [6] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Colon cancer [ICD-11: 2B90] | ||||
Responsed Regulator | LINC01606 (IncRNA) | Suppressor | |||
Pathway Response | Wnt signaling pathway | hsa04310 | |||
Fatty acid metabolism | hsa01212 | ||||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
Cell stemness | |||||
In Vitro Model | SW480 cells | Colon adenocarcinoma | Homo sapiens | CVCL_0546 | |
HT29 cells | Colon cancer | Mus musculus | CVCL_A8EZ | ||
HEK-293T cells | Normal | Homo sapiens | CVCL_0063 | ||
In Vivo Model |
Four-week-old female nude mice were purchased from Cavens (Changzhou, China). Nude mice were randomly divided into four groups. SW480 and HT29 cells infected with sh-LINC01606, Lv-LINC01606 and control vectors were subcutaneously implanted in mice (n = 6 per group), respectively. Tumour volumes (V = length x width2/2) were measured every 3 days, and tumour weights were determined after 4 weeks.
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Response regulation | LINC01606 functions as an oncogene to facilitate tumor cell stemness, proliferation and inhibit ferroptosis and is a promising therapeutic target for colon cancer. Mechanistically, LINC01606 enhanced the expression of stearoyl-CoA desaturase 1 (SCD1), serving as a competing endogenous RNA to modulate miR-423-5p expression, subsequently activating the canonical Wnt/-catenin signaling, and transcription factor binding to IGHM enhancer 3 (TFE3) increased LINC01606 transcription after recruitment to the promoter regions of LINC01606. | ||||
Phospholipid hydroperoxide glutathione peroxidase (GPX4)
In total 4 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [7] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Colon cancer [ICD-11: 2B90] | ||||
Responsed Drug | Honokiol | Investigative | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Glutathione metabolism | hsa00480 | ||||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | SW48 cells | Colon adenocarcinoma | Homo sapiens | CVCL_1724 | |
HT29 cells | Colon cancer | Mus musculus | CVCL_A8EZ | ||
LS174T cells | Colon adenocarcinoma | Homo sapiens | CVCL_1384 | ||
HCT 116 cells | Colon carcinoma | Homo sapiens | CVCL_0291 | ||
HCT-8 cells | Ileocecal adenocarcinoma | Homo sapiens | CVCL_2478 | ||
RKO cells | Colon carcinoma | Homo sapiens | CVCL_0504 | ||
SW480 cells | Colon adenocarcinoma | Homo sapiens | CVCL_0546 | ||
In Vivo Model |
Ten BALB/c nude mice (male, 4 weeks old, 18.0 ± 2.0 g) were randomly divided into two groups for the in vivo xenograft assay. Mice were injected with 5 x 106 RKO cells with stable overexpression GPX4 (described Lv-GPX4 group), control vector (described Lv-NC group). Cells were subcutaneously injected into the right anterior axilla of mice in both groups. Mice then received HNK (0.5 mg/kg/w) by intraperitoneal injection for 4 weeks. The subcutaneous tumor volumes in the nude mice in the two groups were recorded every two days.
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Response regulation | Honokiol reduced the viability of Colon cancer (CC) cell lines by increasing ROS and Fe2+levels. HNK decreased the activity of Glutathione Peroxidase 4 (GPX4) but did not affect system Xc-. Thus, HNK can induce ferroptosis in CC cells by reducing the activity of GPX4. | ||||
Experiment 2 Reporting the Ferroptosis-centered Disease Response by This Target | [8] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Colon carcinoma [ICD-11: 2B90] | ||||
Responsed Regulator | Cellular tumor antigen p53 (TP53) | Driver | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Ubiquitin mediated proteolysis | hsa04120 | ||||
Apoptosis | hsa04210 | ||||
Cell Process | Cell ferroptosis | ||||
Cell apoptosis | |||||
In Vitro Model | HCT 116 cells | Colon carcinoma | Homo sapiens | CVCL_0291 | |
HeLa cells | Endocervical adenocarcinoma | Homo sapiens | CVCL_0030 | ||
HEK-293T cells | Normal | Homo sapiens | CVCL_0063 | ||
HIEC-6 cells | Normal | Homo sapiens | CVCL_6C21 | ||
Response regulation | RRM1 increases the instability of p53 by regulating the physical interaction of p53 with the ubiquitinating enzyme MDM2 and the deubiquitinating enzyme USP11, subsequently suppressing p21 (CDKN1A) and GPX4 in colon carcinoma cells, thereby promoting the accumulation of lipid peroxidation and occurrence of radiation-induced ferroptosis. | ||||
Experiment 3 Reporting the Ferroptosis-centered Disease Response by This Target | [8] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Colon carcinoma [ICD-11: 2B90] | ||||
Responsed Regulator | Cyclin-dependent kinase inhibitor 1 (CDKN1A) | Suppressor | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Ubiquitin mediated proteolysis | hsa04120 | ||||
Apoptosis | hsa04210 | ||||
Cell Process | Cell ferroptosis | ||||
Cell apoptosis | |||||
In Vitro Model | HCT 116 cells | Colon carcinoma | Homo sapiens | CVCL_0291 | |
HeLa cells | Endocervical adenocarcinoma | Homo sapiens | CVCL_0030 | ||
HEK-293T cells | Normal | Homo sapiens | CVCL_0063 | ||
HIEC-6 cells | Normal | Homo sapiens | CVCL_6C21 | ||
Response regulation | RRM1 increases the instability of p53 by regulating the physical interaction of p53 with the ubiquitinating enzyme MDM2 and the deubiquitinating enzyme USP11, subsequently suppressing p21 (CDKN1A) and GPX4, thereby promoting the accumulation of lipid peroxidation and occurrence of radiation-induced ferroptosis in Colon carcinoma. | ||||
Experiment 4 Reporting the Ferroptosis-centered Disease Response by This Target | [8] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Colon carcinoma [ICD-11: 2B90] | ||||
Responsed Regulator | Ribonucleoside-diphosphate reductase large subunit (RRM1) | Driver | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Ubiquitin mediated proteolysis | hsa04120 | ||||
Apoptosis | hsa04210 | ||||
Cell Process | Cell ferroptosis | ||||
Cell apoptosis | |||||
In Vitro Model | HCT 116 cells | Colon carcinoma | Homo sapiens | CVCL_0291 | |
HeLa cells | Endocervical adenocarcinoma | Homo sapiens | CVCL_0030 | ||
HEK-293T cells | Normal | Homo sapiens | CVCL_0063 | ||
HIEC-6 cells | Normal | Homo sapiens | CVCL_6C21 | ||
Response regulation | RRM1 increases the instability of p53 by regulating the physical interaction of p53 with the ubiquitinating enzyme MDM2 and the deubiquitinating enzyme USP11, subsequently suppressing p21 (CDKN1A) and GPX4, thereby promoting the accumulation of lipid peroxidation and occurrence of radiation-induced ferroptosis in Colon carcinoma. | ||||
Beclin-1 (BECN1)
In total 1 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [2] | ||||
Target for Ferroptosis | Driver | ||||
Responsed Disease | Colon carcinoma [ICD-11: 2B90] | ||||
Responsed Drug | Sulfasalazine | Investigative | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
AMPK signaling pathway | hsa04152 | ||||
Autophagy | hsa04140 | ||||
Cell Process | Cell ferroptosis | ||||
Cell autophagy | |||||
In Vitro Model | HCT 116 cells | Colon carcinoma | Homo sapiens | CVCL_0291 | |
PANC-1 cells | Pancreatic ductal adenocarcinoma | Homo sapiens | CVCL_0480 | ||
HT-1080 cells | Fibrosarcoma | Homo sapiens | CVCL_0317 | ||
Calu-1 cells | Lung squamous cell carcinoma | Homo sapiens | CVCL_0608 | ||
HeLa cells | Endocervical adenocarcinoma | Homo sapiens | CVCL_0030 | ||
HEK-293T cells | Normal | Homo sapiens | CVCL_0063 | ||
In Vivo Model |
To generate murine subcutaneous tumors, 5 x 106 HCT116, CX-1, or HT1080 cells in 100 ul phosphate buffered saline (PBS; Thermo Fisher Scientific, AM9625) were injected subcutaneously right of the dorsal midline in athymic nude immunodeficient mice (six- to eight-week-old, female). To generate orthotopic tumors, 1 x 106 KPC cells in 10 ul PBS were surgically implanted into the pancreases of immunocompetent C57BL/6J mice (six- to eight-week-old, female).
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Response regulation | BECN1 plays a novel role in lipid peroxidation that could be exploited to improve anticancer therapy by the induction of ferroptosis in Colon cancer. Mechanistically, phosphorylation of BECN1 at Ser90/93/96 by PRKAA/AMPK contributes to the formation of a BECN1-SLC7A11 complex and system Xc-inhibition. Knockdown of BECN1 by shRNA inhibits ferroptosis induced by system X-c- inhibitors (e.g., erastin, sulfasalazine, and sorafenib). | ||||
References