Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10040)
Regulator Name Frizzled-7 (FZD7)
Synonyms
FzE3
    Click to Show/Hide
Gene Name FZD7
Gene ID 8324
Regulator Type Protein coding
Uniprot ID O75084
Sequence
MRDPGAAAPLSSLGLCALVLALLGALSAGAGAQPYHGEKGISVPDHGFCQPISIPLCTDI
AYNQTILPNLLGHTNQEDAGLEVHQFYPLVKVQCSPELRFFLCSMYAPVCTVLDQAIPPC
RSLCERARQGCEALMNKFGFQWPERLRCENFPVHGAGEICVGQNTSDGSGGPGGGPTAYP
TAPYLPDLPFTALPPGASDGRGRPAFPFSCPRQLKVPPYLGYRFLGERDCGAPCEPGRAN
GLMYFKEEERRFARLWVGVWSVLCCASTLFTVLTYLVDMRRFSYPERPIIFLSGCYFMVA
VAHVAGFLLEDRAVCVERFSDDGYRTVAQGTKKEGCTILFMVLYFFGMASSIWWVILSLT
WFLAAGMKWGHEAIEANSQYFHLAAWAVPAVKTITILAMGQVDGDLLSGVCYVGLSSVDA
LRGFVLAPLFVYLFIGTSFLLAGFVSLFRIRTIMKHDGTKTEKLEKLMVRIGVFSVLYTV
PATIVLACYFYEQAFREHWERTWLLQTCKSYAVPCPPGHFPPMSPDFTVFMIKYLMTMIV
GITTGFWIWSGKTLQSWRRFYHRLSHSSKGETAV

    Click to Show/Hide
Family G-protein coupled receptor Fz/Smo family
Function
Receptor for Wnt proteins. Most frizzled receptors are coupled to the beta-catenin canonical signaling pathway, which leads to the activation of disheveled proteins, inhibition of GSK-3 kinase, nuclear accumulation of beta-catenin and activation of Wnt target genes. A second signaling pathway involving PKC and calcium fluxes has been seen for some family members, but it is not yet clear if it represents a distinct pathway or if it can be integrated in the canonical pathway, as PKC seems to be required for Wnt-mediated inactivation of GSK-3 kinase. Both pathways seem to involve interactions with G-proteins. Activation by WNT8 induces expression of beta-catenin target genes. Following ligand activation, binds to CCDC88C/DAPLE which displaces DVL1 from FZD7 and leads to inhibition of canonical Wnt signaling, activation of G-proteins by CCDC88C and triggering of non-canonical Wnt responses. May be involved in transduction and intercellular transmission of polarity information during tissue morphogenesis and/or in differentiated tissues.

    Click to Show/Hide
HGNC ID
HGNC:4045
KEGG ID hsa:8324
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
FZD7 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
Phospholipid hydroperoxide glutathione peroxidase (GPX4) [Suppressor]
 Target Info 
In total 2 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Target for Ferroptosis Suppressor
Responsed Disease Ovarian cancer ICD-11: 2C73
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 HOSE 96-9-98 cells Normal Homo sapiens CVCL_UW70
HO8910 cells Endocervical adenocarcinoma Homo sapiens CVCL_6868
SK-OV-3 cells Ovarian serous cystadenocarcinoma Homo sapiens CVCL_0532
HEK-293T cells Normal Homo sapiens CVCL_0063
Response regulation FZD7 was a direct target of miR-1-3p, which inhibited the expression of FZD7 by binding to the 3'-untranslated region (3'UTR) site of FZD7. In ovarian cancer tissues, overexpression of FZD7 reduced the sensitivity of platinum-resistant ovarian cancer cells to ferroptosis by up-regulating GPX4 expression.
Experiment 2 Reporting the Ferroptosis Target of This Regulator [2]
Target for Ferroptosis Suppressor
Responsed Disease Ovarian cancer ICD-11: 2C73
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 SK-OV-3 cells Ovarian serous cystadenocarcinoma Homo sapiens CVCL_0532
OVCAR-3 cells Ovarian serous adenocarcinoma Homo sapiens CVCL_0465
OVCAR5 cells Ovarian serous adenocarcinoma Homo sapiens CVCL_1628
COV362 cells Ovarian serous adenocarcinoma Homo sapiens CVCL_2420
FT190 cells Normal Homo sapiens CVCL_UH57
PEO1 cells Metastasis of ovarian carcinoma Homo sapiens CVCL_2686
PEO4 cells Ovarian cystadenocarcinoma Homo sapiens CVCL_2690
In Vivo Model
To develop platinum resistant OC cells in vivo, female (6-8 weeks old) athymic nude mice (Foxn1nu, Envigo) were injected subcutaneously (s.c.) with 2 million SKOV3 or OVCAR3 cells, or intraperitoneally (i.p.) with 2 million OVCAR5 cells to induce tumors.

    Click to Show/Hide
Response regulation Overexpression of FZD7 activated the oncogenic factor Tp63, driving upregulation of glutathione metabolism pathways, including glutathione peroxidase 4 (GPX4), which protected cells from chemotherapy-induced oxidative stress. FZD7 platinum-tolerant ovarian cancer cells were more sensitive and underwent ferroptosis after treatment with GPX4 inhibitors.
Ovarian cancer [ICD-11: 2C73]
 Disease Info 
In total 2 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Frizzled-7 (FZD7) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 HOSE 96-9-98 cells Normal Homo sapiens CVCL_UW70
HO8910 cells Endocervical adenocarcinoma Homo sapiens CVCL_6868
SK-OV-3 cells Ovarian serous cystadenocarcinoma Homo sapiens CVCL_0532
HEK-293T cells Normal Homo sapiens CVCL_0063
Response regulation FZD7 was a direct target of miR-1-3p, which inhibited the expression of FZD7 by binding to the 3'-untranslated region (3'UTR) site of FZD7. In ovarian cancer tissues, overexpression of FZD7 reduced the sensitivity of platinum-resistant ovarian cancer cells to ferroptosis by up-regulating GPX4 expression.
Experiment 2 Reporting the Ferroptosis-centered Disease Response [2]
Target Regulator Frizzled-7 (FZD7) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 SK-OV-3 cells Ovarian serous cystadenocarcinoma Homo sapiens CVCL_0532
OVCAR-3 cells Ovarian serous adenocarcinoma Homo sapiens CVCL_0465
OVCAR5 cells Ovarian serous adenocarcinoma Homo sapiens CVCL_1628
COV362 cells Ovarian serous adenocarcinoma Homo sapiens CVCL_2420
FT190 cells Normal Homo sapiens CVCL_UH57
PEO1 cells Metastasis of ovarian carcinoma Homo sapiens CVCL_2686
PEO4 cells Ovarian cystadenocarcinoma Homo sapiens CVCL_2690
In Vivo Model
To develop platinum resistant OC cells in vivo, female (6-8 weeks old) athymic nude mice (Foxn1nu, Envigo) were injected subcutaneously (s.c.) with 2 million SKOV3 or OVCAR3 cells, or intraperitoneally (i.p.) with 2 million OVCAR5 cells to induce tumors.

    Click to Show/Hide
Response regulation Overexpression of FZD7 activated the oncogenic factor Tp63, driving upregulation of glutathione metabolism pathways, including glutathione peroxidase 4 (GPX4), which protected cells from chemotherapy-induced oxidative stress. FZD7 platinum-tolerant ovarian cancer cells were more sensitive and underwent ferroptosis after treatment with GPX4 inhibitors.
References
Ref 1 MiR-1-3p enhances the sensitivity of ovarian cancer cells to ferroptosis by targeting FZD7. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2022 Nov 28;47(11):1512-1521. doi: 10.11817/j.issn.1672-7347.2022.210800.
Ref 2 Frizzled-7 Identifies Platinum-Tolerant Ovarian Cancer Cells Susceptible to Ferroptosis. Cancer Res. 2021 Jan 15;81(2):384-399. doi: 10.1158/0008-5472.CAN-20-1488. Epub 2020 Nov 10.