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| MIG7 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Identifiers | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Aliases | Migration inducting gene 7mig-7 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | GeneCards:[1];OMA:- orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
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| Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Migration inducting gene 7 (Mig-7 orMig7) is agene that corresponds to acysteine-rich protein localized to thecell membrane andcytoplasm.[2] It is the first-in-class of novel proteins translated from what are thought to be longNon-coding RNAs.[3]
Induction of Mig-7expression occurs downstream ofEpidermal growth factor/Epidermal growth factor receptor,Cox-2/PGE-2 orHepatocyte growth factor/c-Met activation and signalling.[4][5] Data has shown that Mig-7 expression is specific to human embryonic/fetalcytotrophoblast cells[4][6] and epithelial type cancer cells, while not expressed in normal cells.[4][5][6][7][8][9] Data demonstrate that targeting of Mig-7 simultaneously inhibits more than one cancer-progressing pathway while likely sparing normal cells.[4][5][6][9][10]
Mig-7 expression is found on, as well as in, epithelialtumor cells at the primary site, secondary (metastatic) sites, and blood from cancer patients. It is not produced by cells of normal human tissues or by cells from patients with inflammation but is expressed by epithelial precancerous andmalignant cells.[4][5][9] It is also expressed in fetal/embryonic cytotrophoblast cells of earlyplacenta.[4][6]
Mig-7 expression increases in malignant cancers. There is a high sensitivity and specificity of Mig-7 detection in breast (98% n=48 of 49), uterine (100% n=49), gastric (94.5% n=104 of 110) and lung (100% n=89) cancers.[5][8][9]
Mig-7 is thought to promotecarcinoma cell invasion, metastasis and tumor growth throughvasculogenic mimicry,[10] a process where tumor cells form channels for fluids to flow through.[11] It also promotesepithelial–mesenchymal transition (EMT), a key developmental program that is often activated during, and required for, cancer invasion/metastasis. Mig-7 induces EMT throughhyperactivation ofAkt and extracellular regulated KinaseERK1/2 by inhibiting the tumor suppressorprotein phosphate 2A.[5][12]
Mig-7 has been associated with signaling pathways downstream of epithelial type cancer-promoting kinases. It is expressed prior toTWIST,[13] the previously named “master regulator” of EMT.[14] It has also been shown to promote tumorneovascularization.[4][7][8][10]
Cancer cell metabolism (also known as oxidative glycolysis or theWarburg effect) is a proposed cancer target and is likely regulated by Mig-7 through its hyperactivation of Akt.[5]
Targeting of Mig-7 with Mig-7-specific peptides significantly stimulatesbreast cancer patients’ immune cells’ killing of breast carcinoma cellsex vivo.[5] Targeting withantibody generated to the peptide representing the first nine amino acids of Mig-7 detects cells expressing this protein and significantly inhibits carcinoma cell invasion in vitro. Targeting with shorthairpin RNA, specific to decrease Mig-7 protein levels, inhibits carcinoma cell invasion and metastasis as well as returns ERK1/2, Akt, GSK, and S6 kinase to normalphosphorylation states through reactivation of PP2A.[4][5]