TITLE

Insulin activates the insulin receptor to downregulate the PTEN tumour suppressor

AUTHOR(S)
Liu, J; Visser-Grieve, S; Boudreau, J; Yeung, B; Lo, S; Chamberlain, G; Yu, F; Sun, T; Papanicolaou, T; Lam, A; Yang, X; Chin-Sang, I
PUB. DATE
July 2014
SOURCE
Oncogene;7/17/2014, Vol. 33 Issue 29, p3878
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Insulin and insulin-like growth factor-1 signaling have fundamental roles in energy metabolism, growth and development. Recent research suggests hyperactive insulin receptor (IR) and hyperinsulinemia are cancer risk factors. However, the mechanisms that account for the link between the hyperactive insulin signaling and cancer risk are not well understood. Here we show that an insulin-like signaling inhibits the DAF-18/(phosphatase and tensin homolog) PTEN tumour suppressor in Caenorhabditis elegans and that this regulation is conserved in human breast cancer cells. We show that inhibiting the IR increases PTEN protein levels, while increasing insulin signaling decreases PTEN protein levels. Our results show that the kinase region of IRβ subunit physically binds to PTEN and phosphorylates on Y27 and Y174. Our genetic results also show that DAF-2/IR negatively regulates DAF-18/PTEN during C. elegans axon guidance. As PTEN is an important tumour suppressor, our results therefore suggest a possible mechanism for increased cancer risk observed in hyperinsulinemia and hyperactive IR individuals.
ACCESSION #
97069195

 

Related Articles

  • Insulin Receptor Expression in Clear Cell Renal Cell Carcinoma and Its Relation to Prognosis. Lkhagvadorj, Sayamaa; Sung Soo Oh; Mi-Ra Lee; Jae Hung Jung; Hyun Chul Chung; Seung-Kuy Cha; Minseob Eom // Yonsei Medical Journal;Jul2014, Vol. 55 Issue 4, p861 

    Purpose: Both insulin and insulin-like growth factor (IGF)-1 signaling are key regulators of energy metabolism, cellular growth, proliferation, and survival. The IGF-1 receptor (IGF-1R) is overexpressed in most types of human cancers including renal cell carcinoma (RCC) with poor prognosis....

  • Differential Activation of Wnt-β-Catenin Pathway in Triple Negative Breast Cancer Increases MMP7 in a PTEN Dependent Manner. Dey, Nandini; Young, Brandon; Abramovitz, Mark; Bouzyk, Mark; Barwick, Benjamin; De, Pradip; Leyland-Jones, Brian // PLoS ONE;Oct2013, Vol. 8 Issue 10, p1 

    Mutations of genes in tumor cells of Triple Negative subset of Breast Cancer (TNBC) deregulate pathways of signal transduction. The loss of tumor suppressor gene PTEN is the most common first event associated with basal-like subtype (Martins, De, Almendro, Gonen, and Park, 2012). Here we report...

  • The Functional Variant in the 3'UTR of IGF1 with the Risk of Gastric Cancer in a Chinese Population. Jiang, Haiqiang; Wang, Huiyun; Ge, Fengyuan; Wu, Lamei; Wang, Xiao; Chen, Shengxia // Cellular Physiology & Biochemistry (Karger AG);Jun2015, Vol. 36 Issue 3, p884 

    Background/Aims: IGF-1 can act as an endocrine hormone and its signaling server as essential roles in regulating tumorigenesis. Polymorphisms in IGF-1 have been reported associated bad prognosis of with human cancer, but their association with the risk of human gastric cancer (GC) has not been...

  • Insulin Receptor Expression in Clear Cell Renal Cell Carcinoma and Its Relation to Prognosis. Lkhagvadorj, Sayamaa; Sung Soo Oh; Mi-Ra Lee; Jae Hung Jung; Hyun Chul Chung; Seung-Kuy Cha; Minseob Eom // Yonsei Medical Journal;Jun2014, Vol. 55 Issue 4, p861 

    Purpose: Both insulin and insulin-like growth factor (IGF)-1 signaling are key regulators of energy metabolism, cellular growth, proliferation, and survival. The IGF-1 receptor (IGF-1R) is overexpressed in most types of human cancers including renal cell carcinoma (RCC) with poor prognosis....

  • Metabolic triad in brain aging: mitochondria, insulin/IGF-1 signalling and JNK signalling. Yin, Fei; Jiang, Tianyi; Cadenas, Enrique // Biochemical Society Transactions;Feb2013, Vol. 41 Issue 1, p101 

    Mitochondria generate second messengers, such as H2O2, that are involved in the redox regulation of cell signalling and their function is regulated by several cytosolic signalling pathways. IIS [insulin/IGF1 (insulin-like growth factor 1) signalling] in the brain proceeds mainly through the PI3K...

  • Inhibition of IRS-1 by hepatitis C virus infection leads to insulin resistance in a PTEN-dependent manner. Ting-ting Gao; Zhao-ling Qin; Hao Ren; Ping Zhao; Zhong-tian Qi // Virology Journal;2015, Vol. 12 Issue 1, p1 

    Background: Hepatitis C virus (HCV) infection was recently recognized as an independent risk factor for insulin resistance (IR), the onset phase of type 2 diabetes mellitus (T2DM). Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) negatively regulates PI3K/Akt signaling pathway,...

  • Overexpression of the Insulin Receptor Isoform A Promotes Endometrial Carcinoma Cell Growth. Wang, Chun-Fang; Zhang, Guo; Zhao, Li-Jun; Qi, Wen-Juan; Li, Xiao-Ping; Wang, Jian-Liu; Wei, Li-Hui // PLoS ONE;Aug2013, Vol. 8 Issue 8, p1 

    Epidemiological studies have demonstrated that type 2 diabetes mellitus (T2DM) and hyperinsulinemia are associated closely with endometrial carcinoma risk, although the molecular mechanism remains unclear. Insulin receptor isoformA expression is upregulated in many cancer cells and tissues,...

  • Lack of Association between Insulin Receptor Substrate2 rs1805097 Polymorphism and the Risk of Colorectal and Breast Cancer: A Meta-Analysis. Hu, Yue; Zhou, Min; Zhang, Kai; Kong, Xiangquan; Hu, Xiaoyan; Li, Kang; Liu, Li // PLoS ONE;Jan2014, Vol. 9 Issue 1, p1 

    Background: Insulin receptor substrate-2 (IRS-2), a signaling adaptor protein, was involved in two cancer-related pathways (the phosphatidylinositol 3′-kinase (PI3K) and the extracellular signal-regulated kinase (ERK) pathways). Several studies have evaluated the association between IRS2...

  • Association of Polymorphisms and Haplotypes in the Insulin-Like Growth Factor 1 Receptor (IGF1R) Gene with the Risk of Breast Cancer in Korean Women. Kang, Han-Sung; Ahn, Sei Hyun; Mishra, Siddhartha Kumar; Hong, Kyeong-Man; Lee, Eun Sook; Shin, Kyung Hwan; Ro, Jungsil; Lee, Keun Seok; Kim, Mi Kyung // PLoS ONE;Jan2014, Vol. 9 Issue 1, p1 

    The insulin-like growth factor (IGF) signaling pathway plays an important role in cancer biology. The IGF 1 receptor (IGF1R) overexpression has been associated with a number of hematological neoplasias and solid tumors including breast cancer. However, molecular mechanism involving IGF1R in...

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics