Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10515)
Regulator Name Krueppel-like factor 4 (KLF4)
Synonyms
Epithelial zinc finger protein EZF; Gut-enriched krueppel-like factor
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Gene Name KLF4
Gene ID 9314
Regulator Type Protein coding
Uniprot ID O43474
Sequence
MRQPPGESDMAVSDALLPSFSTFASGPAGREKTLRQAGAPNNRWREELSHMKRLPPVLPG
RPYDLAAATVATDLESGGAGAACGGSNLAPLPRRETEEFNDLLDLDFILSNSLTHPPESV
AATVSSSASASSSSSPSSSGPASAPSTCSFTYPIRAGNDPGVAPGGTGGGLLYGRESAPP
PTAPFNLADINDVSPSGGFVAELLRPELDPVYIPPQQPQPPGGGLMGKFVLKASLSAPGS
EYGSPSVISVSKGSPDGSHPVVVAPYNGGPPRTCPKIKQEAVSSCTHLGAGPPLSNGHRP
AAHDFPLGRQLPSRTTPTLGLEEVLSSRDCHPALPLPPGFHPHPGPNYPSFLPDQMQPQV
PPLHYQGQSRGFVARAGEPCVCWPHFGTHGMMLTPPSSPLELMPPGSCMPEEPKPKRGRR
SWPRKRTATHTCDYAGCGKTYTKSSHLKAHLRTHTGEKPYHCDWDGCGWKFARSDELTRH
YRKHTGHRPFQCQKCDRAFSRSDHLALHMKRHF

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Family Krueppel C2H2-type zinc-finger protein family
Function
Transcription factor; can act both as activator and as repressor. Binds the 5'-CACCC-3' core sequence. Binds to the promoter region of its own gene and can activate its own transcription. Regulates the expression of key transcription factors during embryonic development. Plays an important role in maintaining embryonic stem cells, and in preventing their differentiation. Required for establishing the barrier function of the skin and for postnatal maturation and maintenance of the ocular surface. Involved in the differentiation of epithelial cells and may also function in skeletal and kidney development. Contributes to the down-regulation of p53/TP53 transcription.

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HGNC ID
HGNC:6348
KEGG ID hsa:9314
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
KLF4 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
Browse Drug
Cystine/glutamate transporter (SLC7A11) [Driver; Suppressor]
 Target Info 
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Target for Ferroptosis Suppressor
Responsed Disease Breast cancer ICD-11: 2C60
 Disease Info 
Responsed Drug Polyphyllin III Investigative
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 MDA-MB-231 cells Breast adenocarcinoma Homo sapiens CVCL_0062
Hs-578T cells Invasive breast carcinoma Homo sapiens CVCL_0332
MCF-7 cells Breast carcinoma Homo sapiens CVCL_0031
T-47D cells Invasive breast carcinoma Homo sapiens CVCL_0553
HBL-100 cells Normal Homo sapiens CVCL_4362
BT-549 cells Invasive breast carcinoma Homo sapiens CVCL_1092
MDA-MB-453 cells Breast adenocarcinoma Homo sapiens CVCL_0418
In Vivo Model
MDA-MB-231 xenografts were established in 5 week-old BALB/C nude mice (Shanghai SLAC Laboratory Animal Corporation) by inoculating 1 x 106 cells mixed with Matrigel (BD Biosciences) at a 1:1 ratio into the abdominal mammary fat pad. When the tumor reached 50-100 mm3, the mice were assigned randomly into different treatment groups (DMSO, PPIII, SAS, and PPIII + SAS groups), and each group consisted of 5 mice. PPIII (5 mg/kg/day) and SAS (200 mg/kg/day) were dissolved in dimethyl sulfoxide (DMSO), diluted in PBS, and then intraperitoneally injected into mice at a dose of 10 ml/kg/d once a day.

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Response regulation Polyphyllin III, which is a major saponin extracted fromParis polyphyllarhizomes, exerted its proliferation-inhibitory effect on MDA-MB-231 triple-negative breast cancer cells mainly through ACSL4-mediated lipid peroxidation elevation and ferroptosis induction. Polyphyllin III treatment also induced KLF4-mediated protective upregulation of xCT(SLC7A11), which is the negative regulator of ferroptosis.
Breast cancer [ICD-11: 2C60]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Krueppel-like factor 4 (KLF4) Protein coding
 Regulator Info 
Responsed Drug Polyphyllin III Investigative
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 MDA-MB-231 cells Breast adenocarcinoma Homo sapiens CVCL_0062
Hs-578T cells Invasive breast carcinoma Homo sapiens CVCL_0332
MCF-7 cells Breast carcinoma Homo sapiens CVCL_0031
T-47D cells Invasive breast carcinoma Homo sapiens CVCL_0553
HBL-100 cells Normal Homo sapiens CVCL_4362
BT-549 cells Invasive breast carcinoma Homo sapiens CVCL_1092
MDA-MB-453 cells Breast adenocarcinoma Homo sapiens CVCL_0418
In Vivo Model
MDA-MB-231 xenografts were established in 5 week-old BALB/C nude mice (Shanghai SLAC Laboratory Animal Corporation) by inoculating 1 x 106 cells mixed with Matrigel (BD Biosciences) at a 1:1 ratio into the abdominal mammary fat pad. When the tumor reached 50-100 mm3, the mice were assigned randomly into different treatment groups (DMSO, PPIII, SAS, and PPIII + SAS groups), and each group consisted of 5 mice. PPIII (5 mg/kg/day) and SAS (200 mg/kg/day) were dissolved in dimethyl sulfoxide (DMSO), diluted in PBS, and then intraperitoneally injected into mice at a dose of 10 ml/kg/d once a day.

    Click to Show/Hide
Response regulation Polyphyllin III, which is a major saponin extracted fromParis polyphyllarhizomes, exerted its proliferation-inhibitory effect on MDA-MB-231 triple-negative breast cancer cells mainly through ACSL4-mediated lipid peroxidation elevation and ferroptosis induction. Polyphyllin III treatment also induced KLF4-mediated protective upregulation of xCT(SLC7A11), which is the negative regulator of ferroptosis.
Polyphyllin III [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 Cystine/glutamate transporter (SLC7A11) Driver; Suppressor
 Target Info 
Responsed Disease Breast cancer ICD-11: 2C60
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 MDA-MB-231 cells Breast adenocarcinoma Homo sapiens CVCL_0062
Hs-578T cells Invasive breast carcinoma Homo sapiens CVCL_0332
MCF-7 cells Breast carcinoma Homo sapiens CVCL_0031
T-47D cells Invasive breast carcinoma Homo sapiens CVCL_0553
HBL-100 cells Normal Homo sapiens CVCL_4362
BT-549 cells Invasive breast carcinoma Homo sapiens CVCL_1092
MDA-MB-453 cells Breast adenocarcinoma Homo sapiens CVCL_0418
In Vivo Model
MDA-MB-231 xenografts were established in 5 week-old BALB/C nude mice (Shanghai SLAC Laboratory Animal Corporation) by inoculating 1 x 106 cells mixed with Matrigel (BD Biosciences) at a 1:1 ratio into the abdominal mammary fat pad. When the tumor reached 50-100 mm3, the mice were assigned randomly into different treatment groups (DMSO, PPIII, SAS, and PPIII + SAS groups), and each group consisted of 5 mice. PPIII (5 mg/kg/day) and SAS (200 mg/kg/day) were dissolved in dimethyl sulfoxide (DMSO), diluted in PBS, and then intraperitoneally injected into mice at a dose of 10 ml/kg/d once a day.

    Click to Show/Hide
Response regulation Polyphyllin III, which is a major saponin extracted fromParis polyphyllarhizomes, exerted its proliferation-inhibitory effect on MDA-MB-231 triple-negative breast cancer cells mainly through ACSL4-mediated lipid peroxidation elevation and ferroptosis induction. Polyphyllin III treatment also induced KLF4-mediated protective upregulation of xCT(SLC7A11), which is the negative regulator of ferroptosis.
References
Ref 1 Polyphyllin -Induced Ferroptosis in MDA-MB-231 Triple-Negative Breast Cancer Cells can Be Protected Against by KLF4-Mediated Upregulation of xCT. Front Pharmacol. 2021 May 10;12:670224. doi: 10.3389/fphar.2021.670224. eCollection 2021.