Immunohistochemical expression of GCIP in breast carcinoma: relationship with tumour grade, disease‐free survival, mucinous differentiation and response to chemotherapy

Chen, W. C.; Su, Pei-Fang; Jin, Ying; Chang, Ming; Chang, Ta-Yuan

doi:10.1111/j.1365-2559.2008.03154.x

Cited by 8 publications

(13 citation statements)

References 19 publications

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“…Numerous studies have demonstrated that GCIP functions as a tumor suppressor and is down-regulated in various cancers, [6][7][8][9][10][11][12][13] suggesting that repression of GCIP could promote tumor progression. However, the molecular mechanism responsible for down-regulating GCIP expression in cancer and the function(s) through which GCIP suppresses tumor progression were previously unknown.…”

Section: Discussionmentioning

confidence: 99%

MEK2 is a critical modulating mechanism to down‐regulate GCIP stability and function in cancer cells

et al. 2019

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Loss of tumor suppressor activity and upregulation of oncogenic pathways simultaneously contribute to tumorigenesis. Expression of the tumor suppressor, GCIP (Grap2-and cyclin D1-interacting protein), is usually reduced or lost in advanced cancers, as seen in both mouse tumor models and human cancer patients. However, no previous study has examined how cancer cells down-regulate GCIP expression.In this study, we first validate the tumor suppressive function of GCIP using clinical gastric cancer tissues and online database analysis. We then reveal a novel mechanism whereby MEK2 directly interacts with and phosphorylates GCIP at its Ser313 and Ser356 residues to promote the turnover of GCIP by ubiquitin-mediated proteasomal degradation. We also reveal that decreased GCIP stability enhances cell proliferation and promotes cancer cell migration and invasion. Taken together, these findings provide a more comprehensive view of GCIP in tumorigenesis and suggest that the oncogenic MEK/ERK signaling pathway negatively regulates the protein level of GCIP to promote cell proliferation and migration. K E Y W O R D SGCIP, MEK2, tumor suppressor, ubiquitination

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Section: Discussionmentioning

confidence: 99%

MEK2 is a critical modulating mechanism to down‐regulate GCIP stability and function in cancer cells

et al. 2019

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“…Growing evidence indicates that the GCIP is a novel tumor suppressor in breast, colon and liver cancers [22, 27-29]. However, the precise mechanisms underlying its anti-tumor properties have not been fully elucidated.…”

Section: Discussionmentioning

confidence: 99%

“…Unstained slides were deparaffinized in xylene and rehydrated sequentially in ethanol. Immunohistochemistry analysis of GCIP was performed as previously described[29] and Id1 was described in the Supplementary Data.…”

Section: Methodsmentioning

confidence: 99%

“…Animals were sacrificed 30 or 35 days after inoculation, and tumors were isolated and fixed in 10% natural-buffer formalin (Merck, Whitehouse Station, NJ, USA) for further immunohistochemical staining was performed as previously described [29]. …”

Section: Methodsmentioning

confidence: 99%

“…In addition, expression of GCIP was reduced in several cancer tissues with tumor progression and metastasis, including breast, prostate and colon tumor tissues [22]. Furthermore, decreased expression of GCIP correlates with poor patient prognosis in breast cancer [29]. …”

Section: Introductionmentioning

confidence: 99%

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GCIP functions as a tumor suppressor in non-small cell lung cancer by suppressing Id1-mediated tumor promotion

Chen

Tseng

et al. 2014

Oncotarget

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Grap2 and cyclin D1 interacting protein (GCIP) has been recognized as a putative tumor suppressor, but the molecular mechanisms underlying its anti-tumor properties remain undefined. Here, we report that GCIP is frequently downregulated in non-small cell lung cancer (NSCLC) tissues. Binding assays indicated that inhibitor of DNA binding/differentiation 1 (Id1) interacts with GCIP in the nucleus. Ectopic GCIP expression in the highly invasive NSCLC cell line, H1299, inhibited proliferation, colony formation, invasion and migration, and increased susceptibility to anticancer drugs. Conversely, silencing GCIP expression in the minimally invasive NSCLS cell line, A549, increased proliferation, colony formation, invasion, and migration in vitro, and increased survival and resistance to anticancer drugs. GCIP also suppresses tumorigenicity of NSCLC cells in vivo and GCIP suppresses NSCLC progression is mediated in part by interfering with Id1 signaling, which was confirmed in conditionally induced stable cell lines. In addition, GCIP downregulates the expression of Id1, and GCIP and Id1 are inversely expressed in NSCLC cell lines and specimens. Taken together, these results suggest that GCIP is a potential tumor suppressor in NSCLC and that suppression of Id1-mediated oncogenic properties may be a key mechanism by which GCIP can potently suppress NSCLC tumor progression.

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Maid is a negative regulator of transforming growth factor-β-induced cell migration

2015

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Maternal Id-like molecule (Maid) is a dominant negative helix-loop-helix protein that has been implicated in regulating gene expression as well as cell-cycle progression. Overexpressed Maid was previously shown to inhibit certain cellular responses induced by transforming growth factor-β (TGF-β), such as TGF-β-induced cytostasis and cell motility, but not epithelial-mesenchymal transition (EMT). The role of endogenous Maid in regulating TGF-β signalling, however, has not been elucidated. We have found evidence that endogenous Maid negatively regulates TGF-β-induced cell motility. Maid knockdown enhanced TGF-β-induced cell motility as measured by chamber migration and wound healing assays but did not affect cell motility induced by bone morphogenetic protein (BMP)-4. Endogenous Maid does not appear to be involved in regulating TGF-β-induced cytostasis, resistance to apoptosis or EMT. Notably, Maid expression was induced in the delayed phase (later than 24 h) after TGF-β stimulation whereas the expression of two other negative feedback regulators, Smad7 and SnoN, was induced as early as 1 h after stimulation. These findings indicate that Maid is a unique negative feedback regulator of TGF-β signalling in its mode of action as well as the timing of its induction.

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Immunohistochemical expression of GCIP in breast carcinoma: relationship with tumour grade, disease‐free survival, mucinous differentiation and response to chemotherapy

Cited by 8 publications

References 19 publications

MEK2 is a critical modulating mechanism to down‐regulate GCIP stability and function in cancer cells

MEK2 is a critical modulating mechanism to down‐regulate GCIP stability and function in cancer cells

GCIP functions as a tumor suppressor in non-small cell lung cancer by suppressing Id1-mediated tumor promotion

Maid is a negative regulator of transforming growth factor-β-induced cell migration

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