Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10093)
Regulator Name Cadherin-1 (CDH1)
Synonyms
CDHE, UVO; CAM 120/80; Epithelial cadherin; Uvomorulin; CD_antigen=CD324
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Gene Name CDH1
Gene ID 999
Regulator Type Protein coding
Uniprot ID P12830
Sequence
MGPWSRSLSALLLLLQVSSWLCQEPEPCHPGFDAESYTFTVPRRHLERGRVLGRVNFEDC
TGRQRTAYFSLDTRFKVGTDGVITVKRPLRFHNPQIHFLVYAWDSTYRKFSTKVTLNTVG
HHHRPPPHQASVSGIQAELLTFPNSSPGLRRQKRDWVIPPISCPENEKGPFPKNLVQIKS
NKDKEGKVFYSITGQGADTPPVGVFIIERETGWLKVTEPLDRERIATYTLFSHAVSSNGN
AVEDPMEILITVTDQNDNKPEFTQEVFKGSVMEGALPGTSVMEVTATDADDDVNTYNAAI
AYTILSQDPELPDKNMFTINRNTGVISVVTTGLDRESFPTYTLVVQAADLQGEGLSTTAT
AVITVTDTNDNPPIFNPTTYKGQVPENEANVVITTLKVTDADAPNTPAWEAVYTILNDDG
GQFVVTTNPVNNDGILKTAKGLDFEAKQQYILHVAVTNVVPFEVSLTTSTATVTVDVLDV
NEAPIFVPPEKRVEVSEDFGVGQEITSYTAQEPDTFMEQKITYRIWRDTANWLEINPDTG
AISTRAELDREDFEHVKNSTYTALIIATDNGSPVATGTGTLLLILSDVNDNAPIPEPRTI
FFCERNPKPQVINIIDADLPPNTSPFTAELTHGASANWTIQYNDPTQESIILKPKMALEV
GDYKINLKLMDNQNKDQVTTLEVSVCDCEGAAGVCRKAQPVEAGLQIPAILGILGGILAL
LILILLLLLFLRRRAVVKEPLLPPEDDTRDNVYYYDEEGGGEEDQDFDLSQLHRGLDARP
EVTRNDVAPTLMSVPRYLPRPANPDEIGNFIDENLKAADTDPTAPPYDSLLVFDYEGSGS
EAASLSSLNSSESDKDQDYDYLNEWGNRFKKLADMYGGGEDD

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Function
Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterogeneous cell types. CDH1 is involved in mechanisms regulating cell-cell adhesions, mobility and proliferation of epithelial cells. Has a potent invasive suppressor role. It is a ligand for integrin alpha-E/beta-7.

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HGNC ID
HGNC:1748
KEGG ID hsa:999
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
CDH1 can regulate the following target(s), and cause disease/drug response(s). You can browse detail information of target(s) or disease/drug response(s).
Browse Target
Browse Disease
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Unspecific Target [Unspecific Target]
In total 4 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Responsed Disease Head neck squamous cell carcinoma ICD-11: 2D60
 Disease Info 
Responsed Drug 5-Azacitidine Investigative
 Drug Info 
Pathway Response Ferroptosis hsa04216
Cell adhesion molecules hsa04514
Cell Process Cell ferroptosis
In Vitro Model
 AMC-HN-3 cells Laryngeal squamous cell carcinoma Homo sapiens CVCL_5961
HN4 cells Clear cell renal cell carcinoma Homo sapiens CVCL_IS30
HN5 cells Squamous cell carcinoma Homo sapiens CVCL_8128
HN6 cells Tongue squamous cell carcinoma Homo sapiens CVCL_8129
NH-9 cells Tongue squamous cell carcinoma Homo sapiens CVCL_8132
HN-10 cells Laryngeal squamous cell carcinoma Homo sapiens CVCL_8124
In Vivo Model
Six-week-old athymic BALB/c male nude mice (nu/nu) were purchased from OrientBio (Seoul, Republic of Korea). HN9 cells with transfection of CDH1 or control vector or HN4 cells with ZEB1 or control vector were subcutaneously injected into the bilateral flank of nude mice. From the day when gross nodules were detected in tumor implants, mice were subjected to different treatments: vehicle or sulfasalazine (250 mg/kg daily per intraperitoneal route). Each group included six mice.

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Response regulation Histone deacetylase SIRT1 gene silencing or pharmacological inhibition by EX-527 suppressed EMT and consequently decreased ferroptosis, whereas SIRT inducers, resveratrol and SRT1720, increased ferroptosis. In head and neck cancer (HNC) cells with low expression of E-cadherin, the treatment of 5-azacitidine diminished the hypermethylation of CDH1, resulting in increased E-cadherin expression and decreased ferroptosis susceptibility.
Experiment 2 Reporting the Ferroptosis Target of This Regulator [2]
Responsed Disease Meningiomas ICD-11: 2A01
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 CH-157MN cells Meningioma Homo sapiens CVCL_5723
IOMM-Lee cells Intracranial meningioma Homo sapiens CVCL_5779
PM3 (Human meningioma cells)
In Vivo Model
6-week-old male nude mice (Nanjing Medical University Animal Center) were used in this study. There were 6-8 mice/group for survival and tumor growth analysis experiments. For tumor growth analysis, (2 x 106) IOMM-Lee-shMEF2C, IOMM-Lee-shMEF2C-Lv-NF2 or IOMM-Lee-shMEF2C-Lv-Ecad cells were subcutaneously injected to the right flank of the mice to examine the effect of MEF2C, NF2 and E-cadherin status on ferropotosis inducing response in vivo. Erastin, 15 mg/kg in 10% DMSO, or vehicle was administrated intraperitoneally (i.p.) every other day starting at Day 5 after implantation. Tumor diameter was recorded every 5 days starting at Day 10 when the tumors were visible and detectable.

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Response regulation MEF2C was found to drive the expression of both NF2 and E-cadherin. NF2 loss and low CDH1 (E-cadherin) create susceptibility to ferroptosis in meningioma. MEF2C could be a new molecular target in ferroptosis-inducing therapies for meningioma.
Experiment 3 Reporting the Ferroptosis Target of This Regulator [3]
Responsed Disease Gastric cancer ICD-11: 2B72
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Hippo signaling pathway hsa04390
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 SNU-16 cells Gastric adenocarcinoma Homo sapiens CVCL_0076
HEK-293T cells Normal Homo sapiens CVCL_0063
SNU-668 cells Gastric signet ring cell adenocarcinoma Homo sapiens CVCL_5081
In Vivo Model
7.5 X 106 SNU16 sgCDH1 cells expressing a vector, wild-type E-cadherin, or the D291N mutant in 100 ul 1:1 Matrigel: serum-free RPMI were injected into the left flank of athymicnu/numice (Envigo). Tumor growth was monitored every 3 days by caliper. Once tumors reached a mean volume of 150 mm3, mice with each tumor type were randomly grouped into two groups. IKE (MedChemExpress) was resuspended in a solution of 65% D5W (5% dextrose in water), 5% Tween-80, and 30% PEG-400. Mice were then treated daily with either 40 mg/kg IKE or the vehicle via i.p. injection.

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Response regulation E-cadherin (CDH1) is a biomarker predicting the sensitivity to ferroptosis of diffuse-type gastric cancer (DGC) cells, both in primary tumor tissue and in circulation, thus guiding the usage of future ferroptosis-inducing therapeutics for the treatment of DGC.
Experiment 4 Reporting the Ferroptosis Target of This Regulator [4]
Responsed Disease Pulmonary fibrosis ICD-11: CB03
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell adhesion molecules hsa04514
Cell Process Cell ferroptosis
In Vitro Model
 A-549 cells Lung adenocarcinoma Homo sapiens CVCL_0023
In Vivo Model
Forty Sprague-Dawley rats (weight 200 ± 20 g) were obtained from the Experimental Animal Center of Henan Province. The pulmonary fibrosis rat model was established using previously described techniques. The rats were administered a tracheal infusion of bleomycin at a concentration of 5 mg/kg in sterile 0.9% NaCl.

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Response regulation The epithelial-mesenchymal transition (EMT) is an important pathological process in the occurrence of pulmonary fibrosis. SETDB1 regulates the expression of Snai1 by catalyzing the histone H3 lysine 9 trimethylation (H3K9me3) of Snai1, the main transcription factor that initiates the process of EMT, and thus, indirectly regulates E-cadherin (CDH1). And overexpressed SETDB1 alleviated EMT and also caused ferroptosis.
Head neck squamous cell carcinoma [ICD-11: 2D60]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Cadherin-1 (CDH1) Protein coding
 Regulator Info 
Responsed Drug 5-Azacitidine Investigative
 Drug Info 
Pathway Response Ferroptosis hsa04216
Cell adhesion molecules hsa04514
Cell Process Cell ferroptosis
In Vitro Model
 AMC-HN-3 cells Laryngeal squamous cell carcinoma Homo sapiens CVCL_5961
HN4 cells Clear cell renal cell carcinoma Homo sapiens CVCL_IS30
HN5 cells Squamous cell carcinoma Homo sapiens CVCL_8128
HN6 cells Tongue squamous cell carcinoma Homo sapiens CVCL_8129
NH-9 cells Tongue squamous cell carcinoma Homo sapiens CVCL_8132
HN-10 cells Laryngeal squamous cell carcinoma Homo sapiens CVCL_8124
In Vivo Model
Six-week-old athymic BALB/c male nude mice (nu/nu) were purchased from OrientBio (Seoul, Republic of Korea). HN9 cells with transfection of CDH1 or control vector or HN4 cells with ZEB1 or control vector were subcutaneously injected into the bilateral flank of nude mice. From the day when gross nodules were detected in tumor implants, mice were subjected to different treatments: vehicle or sulfasalazine (250 mg/kg daily per intraperitoneal route). Each group included six mice.

    Click to Show/Hide
Response regulation Histone deacetylase SIRT1 gene silencing or pharmacological inhibition by EX-527 suppressed EMT and consequently decreased ferroptosis, whereas SIRT inducers, resveratrol and SRT1720, increased ferroptosis. In head and neck cancer (HNC) cells with low expression of E-cadherin, the treatment of 5-azacitidine diminished the hypermethylation of CDH1, resulting in increased E-cadherin expression and decreased ferroptosis susceptibility.
Meningiomas [ICD-11: 2A01]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [2]
Target Regulator Cadherin-1 (CDH1) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 CH-157MN cells Meningioma Homo sapiens CVCL_5723
IOMM-Lee cells Intracranial meningioma Homo sapiens CVCL_5779
PM3 (Human meningioma cells)
In Vivo Model
6-week-old male nude mice (Nanjing Medical University Animal Center) were used in this study. There were 6-8 mice/group for survival and tumor growth analysis experiments. For tumor growth analysis, (2 x 106) IOMM-Lee-shMEF2C, IOMM-Lee-shMEF2C-Lv-NF2 or IOMM-Lee-shMEF2C-Lv-Ecad cells were subcutaneously injected to the right flank of the mice to examine the effect of MEF2C, NF2 and E-cadherin status on ferropotosis inducing response in vivo. Erastin, 15 mg/kg in 10% DMSO, or vehicle was administrated intraperitoneally (i.p.) every other day starting at Day 5 after implantation. Tumor diameter was recorded every 5 days starting at Day 10 when the tumors were visible and detectable.

    Click to Show/Hide
Response regulation MEF2C was found to drive the expression of both NF2 and E-cadherin. NF2 loss and low CDH1 (E-cadherin) create susceptibility to ferroptosis in meningioma. MEF2C could be a new molecular target in ferroptosis-inducing therapies for meningioma.
Gastric cancer [ICD-11: 2B72]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [3]
Target Regulator Cadherin-1 (CDH1) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Hippo signaling pathway hsa04390
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 SNU-16 cells Gastric adenocarcinoma Homo sapiens CVCL_0076
HEK-293T cells Normal Homo sapiens CVCL_0063
SNU-668 cells Gastric signet ring cell adenocarcinoma Homo sapiens CVCL_5081
In Vivo Model
7.5 X 106 SNU16 sgCDH1 cells expressing a vector, wild-type E-cadherin, or the D291N mutant in 100 ul 1:1 Matrigel: serum-free RPMI were injected into the left flank of athymicnu/numice (Envigo). Tumor growth was monitored every 3 days by caliper. Once tumors reached a mean volume of 150 mm3, mice with each tumor type were randomly grouped into two groups. IKE (MedChemExpress) was resuspended in a solution of 65% D5W (5% dextrose in water), 5% Tween-80, and 30% PEG-400. Mice were then treated daily with either 40 mg/kg IKE or the vehicle via i.p. injection.

    Click to Show/Hide
Response regulation E-cadherin (CDH1) is a biomarker predicting the sensitivity to ferroptosis of diffuse-type gastric cancer (DGC) cells, both in primary tumor tissue and in circulation, thus guiding the usage of future ferroptosis-inducing therapeutics for the treatment of DGC.
Pulmonary fibrosis [ICD-11: CB03]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [4]
Target Regulator Cadherin-1 (CDH1) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell adhesion molecules hsa04514
Cell Process Cell ferroptosis
In Vitro Model
 A-549 cells Lung adenocarcinoma Homo sapiens CVCL_0023
In Vivo Model
Forty Sprague-Dawley rats (weight 200 ± 20 g) were obtained from the Experimental Animal Center of Henan Province. The pulmonary fibrosis rat model was established using previously described techniques. The rats were administered a tracheal infusion of bleomycin at a concentration of 5 mg/kg in sterile 0.9% NaCl.

    Click to Show/Hide
Response regulation The epithelial-mesenchymal transition (EMT) is an important pathological process in the occurrence of pulmonary fibrosis. SETDB1 regulates the expression of Snai1 by catalyzing the histone H3 lysine 9 trimethylation (H3K9me3) of Snai1, the main transcription factor that initiates the process of EMT, and thus, indirectly regulates E-cadherin (CDH1). And overexpressed SETDB1 alleviated EMT and also caused ferroptosis.
5-Azacitidine [Investigative]
 Drug Info 
In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response [1]
Drug for Ferroptosis Suppressor
Response Target Unspecific Target
Responsed Disease Head neck squamous cell carcinoma ICD-11: 2D60
 Disease Info 
Pathway Response Ferroptosis hsa04216
Cell adhesion molecules hsa04514
Cell Process Cell ferroptosis
In Vitro Model
 AMC-HN-3 cells Laryngeal squamous cell carcinoma Homo sapiens CVCL_5961
HN4 cells Clear cell renal cell carcinoma Homo sapiens CVCL_IS30
HN5 cells Squamous cell carcinoma Homo sapiens CVCL_8128
HN6 cells Tongue squamous cell carcinoma Homo sapiens CVCL_8129
NH-9 cells Tongue squamous cell carcinoma Homo sapiens CVCL_8132
HN-10 cells Laryngeal squamous cell carcinoma Homo sapiens CVCL_8124
In Vivo Model
Six-week-old athymic BALB/c male nude mice (nu/nu) were purchased from OrientBio (Seoul, Republic of Korea). HN9 cells with transfection of CDH1 or control vector or HN4 cells with ZEB1 or control vector were subcutaneously injected into the bilateral flank of nude mice. From the day when gross nodules were detected in tumor implants, mice were subjected to different treatments: vehicle or sulfasalazine (250 mg/kg daily per intraperitoneal route). Each group included six mice.

    Click to Show/Hide
Response regulation Histone deacetylase SIRT1 gene silencing or pharmacological inhibition by EX-527 suppressed EMT and consequently decreased ferroptosis, whereas SIRT inducers, resveratrol and SRT1720, increased ferroptosis. In head and neck cancer (HNC) cells with low expression of E-cadherin, the treatment of 5-azacitidine diminished the hypermethylation of CDH1, resulting in increased E-cadherin expression and decreased ferroptosis susceptibility.
References
Ref 1 Epigenetic reprogramming of epithelial-mesenchymal transition promotes ferroptosis of head and neck cancer. Redox Biol. 2020 Oct;37:101697. doi: 10.1016/j.redox.2020.101697. Epub 2020 Aug 28.
Ref 2 MEF2C silencing downregulates NF2 and E-cadherin and enhances Erastin-induced ferroptosis in meningioma. Neuro Oncol. 2021 Dec 1;23(12):2014-2027. doi: 10.1093/neuonc/noab114.
Ref 3 E-cadherin is a biomarker for ferroptosis sensitivity in diffuse gastric cancer. Oncogene. 2023 Mar;42(11):848-857. doi: 10.1038/s41388-023-02599-5. Epub 2023 Jan 30.
Ref 4 Histone methyltransferase SETDB1 inhibits TGF--induced epithelial-mesenchymal transition in pulmonary fibrosis by regulating SNAI1 expression and the ferroptosis signaling pathway. Arch Biochem Biophys. 2022 Jan 15;715:109087. doi: 10.1016/j.abb.2021.109087. Epub 2021 Nov 18.