Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10512)
Regulator Name Dickkopf-related protein 1 (DKK1)
Synonyms
SK
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Gene Name DKK1
Gene ID 22943
Regulator Type Protein coding
Uniprot ID O94907
Sequence
MMALGAAGATRVFVAMVAAALGGHPLLGVSATLNSVLNSNAIKNLPPPLGGAAGHPGSAV
SAAPGILYPGGNKYQTIDNYQPYPCAEDEECGTDEYCASPTRGGDAGVQICLACRKRRKR
CMRHAMCCPGNYCKNGICVSSDQNHFRGEIEETITESFGNDHSTLDGYSRRTTLSSKMYH
TKGQEGSVCLRSSDCASGLCCARHFWSKICKPVLKEGQVCTKHRRKGSHGLEIFQRCYCG
EGLSCRIQKDHHQASNSSRLHTCQRH

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Family Dickkopf family
Function
Antagonizes canonical Wnt signaling by inhibiting LRP5/6 interaction with Wnt and by forming a ternary complex with the transmembrane protein KREMEN that promotes internalization of LRP5/6. DKKs play an important role in vertebrate development, where they locally inhibit Wnt regulated processes such as antero-posterior axial patterning, limb development, somitogenesis and eye formation. In the adult, Dkks are implicated in bone formation and bone disease, cancer and Alzheimer disease. Inhibits the pro-apoptotic function of KREMEN1 in a Wnt-independent manner, and has anti-apoptotic activity (By similarity).

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HGNC ID
HGNC:2891
KEGG ID hsa:22943
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
DKK1 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
Nuclear factor erythroid 2-related factor 2 (NFE2L2) [Suppressor; Marker]
 Target Info 
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Target for Ferroptosis Marker/Suppressor
Responsed Disease Melanoma ICD-11: 2C30
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 PIG1 cells Normal Homo sapiens CVCL_S410
A-375 cells Amelanotic melanoma Homo sapiens CVCL_0132
G-361 cells Melanoma Homo sapiens CVCL_1220
HS1-CLS cells Skin sarcoma Homo sapiens CVCL_5978
IGR-1 cells Cutaneous melanoma Homo sapiens CVCL_1303
MeWo cells Melanoma Homo sapiens CVCL_0445
NIS-G cells Melanoma Homo sapiens CVCL_6005
WS1-CLS cells Skin sarcoma Homo sapiens CVCL_6211
KMM-L1 cells Normal Mus musculus CVCL_XB77
In Vivo Model
NU/NU nude mice were purchased from Hunan Slac Laboratory Animals Co., Ltd. (Changsha, China). Melanoma cells (5 x 106) were injected subcutaneously into the left posterior side of 7-week-old immunodeficient female mice. The tumor growth was monitored by measuring the length (L) and width (W) of the tumor. Tumor volume = 1/2 (length x width2). When the tumor volume reached about 50 mm3, mice were randomly assigned into 8 groups (n = 6) and given intraperitoneal injection of erastin for 20 days. Erastin was dissolved in 5% DMSO + corn oil (C8267, Sigma) in the test tube heated at 37 and gently shaken before use.

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Response regulation MiR-130b-3p is able to inhibit the ferroptosis induced by erastin or RSL3 in melanoma cells by targeting DKK1 and subsequent activation of Nrf2/HO-1 pathway.
Melanoma [ICD-11: 2C30]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Dickkopf-related protein 1 (DKK1) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 PIG1 cells Normal Homo sapiens CVCL_S410
A-375 cells Amelanotic melanoma Homo sapiens CVCL_0132
G-361 cells Melanoma Homo sapiens CVCL_1220
HS1-CLS cells Skin sarcoma Homo sapiens CVCL_5978
IGR-1 cells Cutaneous melanoma Homo sapiens CVCL_1303
MeWo cells Melanoma Homo sapiens CVCL_0445
NIS-G cells Melanoma Homo sapiens CVCL_6005
WS1-CLS cells Skin sarcoma Homo sapiens CVCL_6211
KMM-L1 cells Normal Mus musculus CVCL_XB77
In Vivo Model
NU/NU nude mice were purchased from Hunan Slac Laboratory Animals Co., Ltd. (Changsha, China). Melanoma cells (5 x 106) were injected subcutaneously into the left posterior side of 7-week-old immunodeficient female mice. The tumor growth was monitored by measuring the length (L) and width (W) of the tumor. Tumor volume = 1/2 (length x width2). When the tumor volume reached about 50 mm3, mice were randomly assigned into 8 groups (n = 6) and given intraperitoneal injection of erastin for 20 days. Erastin was dissolved in 5% DMSO + corn oil (C8267, Sigma) in the test tube heated at 37 and gently shaken before use.

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Response regulation MiR-130b-3p is able to inhibit the ferroptosis induced by erastin or RSL3 in melanoma cells by targeting DKK1 and subsequent activation of Nrf2/HO-1 pathway.
References
Ref 1 Suppressive role of microRNA-130b-3p in ferroptosis in melanoma cells correlates with DKK1 inhibition and Nrf2-HO-1 pathway activation. Hum Cell. 2021 Sep;34(5):1532-1544. doi: 10.1007/s13577-021-00557-5. Epub 2021 Jun 11.