Evidence that MIG-6 is a tumor-suppressor gene

Zhang, Y.-W.; Staal, Ben; Su, Yingchun; Swiatek, Pamela J.; Zhao, Ping; Cao, Brain; Resau, James H.; Sigler, Robert E.; Bronson, Roderick T.; Woude, George F. Vande

doi:10.1038/sj.onc.1209790

Cited by 128 publications

(158 citation statements)

References 34 publications

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“…This tumor suppressor function in mice (23,24) is also observed in humans (25,26). The fact that Mig-6 was found to be a SRC-1-dependent PR-responsive gene prompted us to investigate its function in the murine endometrium.…”

Section: Identification Of P4 and Src-1 Regulated Genes Using Microarraymentioning

confidence: 80%

“…Ablation of Mig-6 in mice leads to animals with epithelial hyperplasia, adenoma, and adenocarcinoma in organs like the lung, gallbladder, and bile duct (24). This tumor suppressor function in mice (23,24) is also observed in humans (25,26).…”

Section: Identification Of P4 and Src-1 Regulated Genes Using Microarraymentioning

confidence: 98%

“…Decreased expression of Mig-6 is observed in human breast carcinomas that correlate with reduced overall survival of breast cancer patients (27,28). Mig-6 is mutated in human non-small-cell lung cancer (NSCLC) cell lines NCI-H226 and NCI-H 322M and in one primary human lung cancer (24). Recently, altered Mig-6 expression has been observed in endometrial RNA taken from women with endometriosis (29).…”

mentioning

confidence: 99%

“…Sustained Mig-6 expression is thought to trigger cells to initiate hypertrophy in chronic pathological conditions, such as diabetes and hypertension (21,22). Ablation of Mig-6 in mice has led to the development of animals with epithelial hyperplasia, adenoma, and adenocarcinomas in organs, such as the lung, gallbladder, and bile duct (23,24). Mig-6 is located on human chromosome 1p36, a locus frequently associated with human cancer (25,26).…”

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confidence: 99%

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Mig-6 modulates uterine steroid hormone responsiveness and exhibits altered expression in endometrial disease

Jeong

Lee

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

118

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Normal endometrial function requires a balance of progesterone (P4) and estrogen (E2) effects. An imbalance caused by increased E2 action and/or decreased P4 action can result in abnormal endometrial proliferation and, ultimately, endometrial adenocarcinoma, the fourth most common cancer in women. We have identified mitogen-inducible gene 6 (Mig-6) as a downstream target of progesterone receptor (PR) and steroid receptor coactivator (SRC-1) action in the uterus. Here, we demonstrate that absence of Mig-6 in mice results in the inability of P4 to inhibit E2-induced uterine weight gain and E2-responsive target genes expression. At 5 months of age, the absence of Mig-6 results in endometrial hyperplasia. Ovariectomized Mig-6 d/d mice exhibit this hyperplastic phenotype in the presence of E2 and P4 but not without ovarian hormone. Ovariectomized Mig-6 d/d mice treated with E2 developed invasive endometrioid-type endometrial adenocarcinoma. Importantly, the observation that endometrial carcinomas from women have a significant reduction in MIG-6 expression provides compelling support for an important growth regulatory role for Mig-6 in the uterus of both humans and mice. This demonstrates the Mig-6 is a critical regulator of the response of the endometrium to E2 in regulating tissue homeostasis. Since Mig-6 is regulated by both PR and SRC-1, this identifies a PR, SRC-1, Mig-6 regulatory pathway that is critical in the suppression of endometrial cancer.estrogen ͉ endometrial cancer ͉ progesterone ͉ progesterone receptor ͉ SRC-1

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Section: Identification Of P4 and Src-1 Regulated Genes Using Microarraymentioning

confidence: 80%

Section: Identification Of P4 and Src-1 Regulated Genes Using Microarraymentioning

confidence: 98%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Mig-6 modulates uterine steroid hormone responsiveness and exhibits altered expression in endometrial disease

Jeong

Lee

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

118

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“…Notably, Mig-6 mouse mutants hyperactivate EGFR, leading to MAPK stimulation and the development of benign and malignant tumors of the stomach, colon, biliary tree and lung with enhanced susceptibility to carcinogen-induced skin cancer [106,107]. Mig-6 has also been found to be mutated in nonsmall cell lung cancer (NSCLC) cell lines and rarely in primary lung cancer, suggesting that MIG-6 may also play a role as a tumor suppressor gene in humans [107].…”

Section: Signal Attenuationmentioning

confidence: 99%

The epidermal growth factor receptor family: Biology driving targeted therapeutics

Wieduwilt

Moasser

2008

Cell. Mol. Life Sci.

644

503

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The epidermal growth factor family of receptor tyrosine kinases (ErbBs) plays essential roles in regulating cell proliferation, survival, differentiation and migration. The ErbB receptors carry out both redundant and restricted functions in mammalian development and in the maintenance of tissues in the adult mammal. Loss of regulation of the ErbB receptors underlies many human diseases, most notably cancer. Our understanding of the function and complex regulation of these receptors has fueled the development of targeted therapeutic agents for human malignancies in the last 15 years. Here we review the biology of ErbB receptors, including their structure, signaling, regulation, and roles in development and disease, then briefly touch on their increasing roles as targets for cancer therapy.

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Functional loss of ERBB receptor feedback inhibitor 1 (MIG6) promotes glioblastoma tumorigenesis by aberrant activation of epidermal growth factor receptor (EGFR)

Yi,

Cho,

Kim

et al. 2024

Molecular Oncology

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Dysregulation of epidermal growth factor receptor (EGFR) is one of the most common mechanisms associated with the pathogenesis of various cancers. Mitogen‐inducible gene 6 [MIG6; also known as ERBB receptor feedback inhibitor 1 (ERRFI1)], identified as a feedback inhibitor of EGFR, negatively regulates EGFR by directly inhibiting its kinase activity and facilitating its internalization, subsequently leading to degradation. Despite its proposed role as an EGFR‐dependent tumor suppressor, the functional consequences and clinical relevance in cancer etiology remain incompletely understood. Here, we identify that the stoichiometric balance between MIG6 and EGFR is crucial in promoting EGFR‐dependent oncogenic growth in various experimental model systems. In addition, a subset of ERRFI1 (the official gene symbol of MIG6) mutations exhibit impaired ability to suppress the enzymatic activation of EGFR at multiple levels. In summary, our data suggest that decreased or loss of MIG6 activity can lead to abnormal activation of EGFR, potentially contributing to cellular transformation. We propose that the mutation status of ERRFI1 and the expression levels of MIG6 can serve as additional biomarkers for guiding EGFR‐targeted cancer therapies, including glioblastoma.

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Evidence that MIG-6 is a tumor-suppressor gene

Cited by 128 publications

References 34 publications

Mig-6 modulates uterine steroid hormone responsiveness and exhibits altered expression in endometrial disease

Mig-6 modulates uterine steroid hormone responsiveness and exhibits altered expression in endometrial disease

The epidermal growth factor receptor family: Biology driving targeted therapeutics

Functional loss of ERBB receptor feedback inhibitor 1 (MIG6) promotes glioblastoma tumorigenesis by aberrant activation of epidermal growth factor receptor (EGFR)

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