Migration inducting gene 7
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|, Migration inducting gene 7|
Migration inducting gene 7 (Mig-7 or Mig7) is a gene. The protein is cysteine-rich, and localized to the cell membrane and cytoplasm. It is the first-in-class of novel proteins translated from what are thought to be long Non-coding RNAs.
Induction of Mig-7 expression occurs downstream of Epidermal growth factor/Epidermal growth factor receptor, Cox-2/PGE-2 or Hepatocyte growth factor/c-Met activation and signalling. Data has shown that Mig-7 expression is specific to human embryonic/fetal cytotrophoblast cells and epithelial type cancer cells, while not expressed in normal cells. Data demonstrate that targeting of Mig-7 simultaneously inhibits more than one cancer-progressing pathway while likely sparing normal cells.
Mig-7 expression is found on, as well as in, epithelial tumor 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 and malignant cells. It is also expressed in fetal/embryonic cytotrophoblast cells of early placenta.
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.
Function and role in cancer
Mig-7 is thought to promote carcinoma cell invasion, metastasis and tumor growth through vasculogenic mimicry, a process where tumor cells form channels for fluids to flow through. It also promotes epithelial–mesenchymal transition (EMT), a key developmental program that is often activated during, and required for, cancer invasion/metastasis. Mig-7 induces EMT through hyperactivation of Akt and extracellular regulated Kinase ERK1/2 by inhibiting the tumor suppressor protein phosphate 2A.
Mig-7 has been associated with signaling pathways downstream of epithelial type cancer-promoting kinases. It is expressed prior to TWIST, the previously named “master regulator” of EMT. It has also been shown to promote tumor neovascularization.
Targeting of Mig-7
Targeting of Mig-7 with Mig-7-specific peptides significantly stimulates breast cancer patients’ immune cells’ killing of breast carcinoma cells ex vivo. Targeting with antibody 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 short hairpin 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 normal phosphorylation states through reactivation of PP2A.
- "Human PubMed Reference:".
- Robertson GP (May 2007). "Mig-7 linked to vasculogenic mimicry". Am. J. Pathol. 170 (5): 1454–6. doi:10.2353/ajpath.2007.070127. PMC . PMID 17456752.
- Petty AP, Dick CL, Lindsey JS (May 2008). "Translation of an atypical human cDNA requires fidelity of apurine-pyrimidine repeat region and recoding". Gene. 414 (1-2): 49–59. doi:10.1016/j.gene.2008.02.006. PMID 18378409.
- Ho MY, Liang SM, Hung SW, Liang CM (January 2013). "MIG-7 controls COX-2/PGE2-mediated lung cancer metastasis". Cancer Res. 73 (1): 439–49. doi:10.1158/0008-5472.CAN-12-2220. PMID 23149922.
- Petty AP, Garman KL, Winn VD, Spidel CM, Lindsey JS (May 2007). "Overexpression of carcinoma and embryonic cytotrophoblast cell-specific Mig-7 induces invasion and vessel-like structure formation". Am. J. Pathol. 170 (5): 1763–80. doi:10.2353/ajpath.2007.060969. PMC . PMID 17456780.
- Petty AP, Wright SE, Rewers-Felkins KA, Yenderrozos MA, Vorderstrasse BA, Lindsey JS (August 2009). "Targeting migration inducting gene-7 inhibits carcinoma cell invasion, early primary tumor growth, and stimulates monocyte oncolytic activity". Mol. Cancer Ther. 8 (8): 2412–23. doi:10.1158/1535-7163.MCT-09-0186. PMC . PMID 19671748.
- Crouch S, Spidel CS, Lindsey JS (January 2004). "HGF and ligation of alphavbeta5 integrin induce a novel, cancer cell-specific gene expression required for cell scattering". Exp. Cell Res. 292 (2): 274–87. doi:10.1016/j.yexcr.2003.09.016. PMID 14697335.
- Li WL, Gao Q (November 2012). "[Mig-7 enhances vasculogenic mimicry in gastric cancer cells]". Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi (in Chinese). 28 (11): 1142–5. PMID 23127401.
- Liao S, Gao Q (February 2013). "[Expressions and clinical significance of vasculogenic mimicry and related protein Mig-7 and MMP-2 in gastric carcinoma]". Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi (in Chinese). 29 (2): 194–6. PMID 23388341.
- Phillips TM, Lindsey JS (January 2005). "Carcinoma cell-specific Mig-7: a new potential marker for circulating and migrating cancer cells". Oncol. Rep. 13 (1): 37–44. doi:10.3892/or.13.1.37. PMID 15583799.
- Folberg R, Maniotis AJ (2004). "Vasculogenic mimicry". APMIS. 112 (7-8): 508–25. doi:10.1111/j.1600-0463.2004.apm11207-0810.x. PMID 15563313.
- Weiss MB, Abel EV, Mayberry MM, Basile KJ, Berger AC, Aplin AE (December 2012). "TWIST1 is an ERK1/2 effector that promotes invasion and regulates MMP-1 expression in human melanoma cells". Cancer Res. 72 (24): 6382–92. doi:10.1158/0008-5472.CAN-12-1033. PMC . PMID 23222305.
- Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, Brooks M, Reinhard F, Zhang CC, Shipitsin M, Campbell LL, Polyak K, Brisken C, Yang J, Weinberg RA (May 2008). "The epithelial-mesenchymal transition generates cells with properties of stem cells". Cell. 133 (4): 704–15. doi:10.1016/j.cell.2008.03.027. PMC . PMID 18485877.
- Zheng H, Kang Y (April 2013). "Multilayer control of the EMT master regulators". Oncogene. 33 (14): 1755–63. doi:10.1038/onc.2013.128. PMID 23604123.