The role of insulin receptor substrate (IRS) proteins in oncogenic transformation

Görgişen, Gökhan; Gülaçar, İsmail Musab; Özeş, Osman N.

doi:10.14715/cmb/2017.63.1.1

Cited by 30 publications

(36 citation statements)

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“…Mechanistically, this study identified IRS1 could be directly targeted by miR-126 for downregulation. The reduction of IRS1 was observed both in mRNA and protein levels, suggesting the ability of miR-126 in degradating IRS1 mRNA.IRS1 functions as a key molecule that transmits signals from IGF-1R to downstream pathways such as the PI3K/Akt and MAPK pathways [17]. Overexpression of IRS1 was reported to promote the proliferation of hepatocytes and thus potentially contributed to HCC progression [18,19].…”

Section: Discussionmentioning

confidence: 99%

MiR-126 enhances cisplatin chemosensitivity in hepatocellular carcinoma cells by targeting IRS1

Zuo¹,

Luo²,

Huang³

et al. 2019

Trop. J. Pharm Res

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Purpose: To investigate the potential role of miR-126 in regulating the proliferation and cisplatin chemosensitivity of human hepatocellular carcinoma (HCC) cells. Methods: The expression of miR-126 was evaluated using clinical HCC specimens. MiR-126-mediated downregulation of Insulin Receptor Substrate 1 (IRS1) was determined by qRT-PCR, western blot and luciferase reporter assay. Cell Counting Kit-8 (CCK8) and colony formation assays were performed to examine the proliferation of HCC cells. Results: Decreased expression of miR126 was found in HCC tumors and was correlated with poor survival in HCC patients. In HCC cells, miR-126 targeted IRS1 for downregulation, through which miR-126 suppressed the growth of HCC cells and desensitized HCC cells to cisplatin treatment. Conclusion: MiR-126a impairs the proliferation and cisplatin chemoresistance of HCC cells by targeting IRS1.

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Section: Discussionmentioning

confidence: 99%

MiR-126 enhances cisplatin chemosensitivity in hepatocellular carcinoma cells by targeting IRS1

Zuo¹,

Luo²,

Huang³

et al. 2019

Trop. J. Pharm Res

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“…Increased expression levels of IGF-1R and IRS1 are associated with many human malignancies which implies that both of the proteins have a pivotal role in carcinogenesis (9,21,22). Recent studies have also shown that IGF-1R and IRS1 are responsible for the development of chemo-and radioresistance in cancer cells but their molecular mechanisms have not been discovered yet (23).…”

Section: Discussionmentioning

confidence: 99%

“…Its expression is induced by many oncogenes such as MAPK and AKT during carcinogenesis and hypoxia (31). During insulin signaling, glucose uptake rates of the cells is regulated by IRS1 proteins through the activation of AKT and translocation of GLUT proteins to the cell membrane (9). GLUT1 expression could be elevated by increased IRS1 expression in A172 cells and this overexpression may cause to reduce the sensitivity to radiotherapy.…”

Section: Discussionmentioning

confidence: 99%

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Overexpression of Insulin Receptor Substrate 1 (IRS1) Promotes Radioresistance in A172 Glioblastoma Cell Line

Görgişen¹,

Çakır²,

Ateş³

et al. 2019

Eastern J Med

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Insulin receptor substrate 1 (IRS1) is the main adaptor molecule in insulin and insulin like growth factor signaling. Increased level of expression of IRS1 and IGF-1R proteins are associated with many human malignancies. They also induced resistance to therapeutic approaches such as chemo-and radiotherapy in cancer treatment however their molecular mechanisms are still unclear. Glioblastoma Multiforme (GBM) is the most common primary brain tumor in adults and radiotherapy has a pivotal role in its treatment. In this study, it is aimed to determine the relationship between IRS1 expression and radiosensitivity of GBM cells. Therefore, A172 cells transfected with pcDNA3.1-HA-tagged human IRS1 gene. Its overexpression was confirmed by western blot. IRS1 overexpressed A172 cells were irradiated with 5,8 and 10 Gray ionizing radiation and their effects on cell viability determined by MTT and clonogenic assay. Our results showed that overexpression of IRS1 led a decrease on sensitivity of the radiation in GBM cel ls. As a conclusion, this study should be confirmed by further molecular analysis and in vivo studies. IRS1 may be a predictive marker of radiosensitivity for GBM.

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“…When IRS1 binds to its receptors, it is phosphorylated on tyrosine residues. Tyrosine phosphorylation of IRS1 induces the activation of PI3K-AKT and Ras-ERK pathways [13]. Transformation capacity of IRS1 was first shown in mouse embryonic fibroblasts and its overexpression is primarily responsible for cell proliferation in breast cancer [4].…”

Section: Introductionmentioning

confidence: 99%

Insulin receptor substrate 1 overexpression promotes survival of glioblastoma cells through AKT1 activation

Görgişen¹,

Yaren²

2020

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Glioblastoma multiforme (GBM) is the most common and malignant type of central nervous system tumours in adults. Strict regulation of glucose homeostasis has a significant role in GBM pathogenesis. Insulin receptor substrate 1 (IRS1) protein is the most important adaptor molecule involved in the regulation of glucose metabolism. It interacts with many cancer-related receptors and its overexpression is strongly associated with cell proliferation and survival. Our study was aimed to understand the role of IRS1 proteins in GBM cell viability. U-87 MG cells were transfected with pcDNA3.1-flagtagged-human IRS1 expression vector. Insulin induced phosphorylation levels of IRS1, AKT1 and ERK1/2 and Grb2 expression were examined to determine the effects of ectopic IRS1 overexpression on insulin signalling and the viability levels of U-87 MG cells were determined by MTT analysis. Overexpression of IRS1 in U-87 MG cells led to an increase in cell viability. Its overexpression also increased Grb2 expression and phosphorylation of AKT1 through elevation of IRS1 tyrosine phosphorylation in IRS1-transfected U-87 MG cells compared to control and mock transfected groups. Our study showed that increased IRS1 expression and activation may promote the cell viability via AKT1 activation. IRS1 signalling may be considered as a therapeutic target for further studies.

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The role of insulin receptor substrate (IRS) proteins in oncogenic transformation

Cited by 30 publications

References 0 publications

MiR-126 enhances cisplatin chemosensitivity in hepatocellular carcinoma cells by targeting IRS1

MiR-126 enhances cisplatin chemosensitivity in hepatocellular carcinoma cells by targeting IRS1

Overexpression of Insulin Receptor Substrate 1 (IRS1) Promotes Radioresistance in A172 Glioblastoma Cell Line

Insulin receptor substrate 1 overexpression promotes survival of glioblastoma cells through AKT1 activation

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