Related Experiment Video

Updated: Jun 2, 2026

Identification and Characterization of Metastatic Factors by Gene Transfer into the Novel RIP-Tag; RIP-tva Murine Model
09:03

Identification and Characterization of Metastatic Factors by Gene Transfer into the Novel RIP-Tag; RIP-tva Murine Model

Published on: October 16, 2017

Depletion of insulin receptor substrate 2 reverses oncogenic transformation induced by v-src

Hong-zhi Sun1, Lin Xu, Bo Zhou

  • 1Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Medical School of Xi'an Jiaotong University, Xi'an 710061, China. sunhongzhi@mail.xjtu.edu.cn

Acta Pharmacologica Sinica
|May 3, 2011
PubMed
Abstract

Insights

Silencing insulin receptor substrate 2 (IRS-2) reversed v-src induced oncogenic transformation by inhibiting cell growth and promoter activity. IRS-2 nuclear translocation is critical for v-src-driven cell transformation.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • The v-src oncoprotein drives cellular transformation and oncogenesis.
  • Insulin receptor substrate 2 (IRS-2) is implicated in cell growth and survival pathways.

Purpose of the Study:

  • To elucidate the role of IRS-2 in v-src-mediated oncogenic transformation.
  • To investigate the molecular mechanisms by which IRS-2 contributes to transformation.

Main Methods:

  • Small interfering RNAs (siRNAs) were used to deplete IRS-2.
  • Subcellular fractionation, confocal microscopy, and immunoprecipitation assessed IRS-2 nuclear translocation and v-src interaction.
  • Luciferase assays measured cyclin D1 and rDNA promoter activity.

Main Results:

  • IRS-2 depletion inhibited v-src-induced cell growth and reversed oncogenic transformation.
  • IRS-2 interacted with v-src through its PI3-K binding sites, crucial for transformation.
  • Nuclear IRS-2 occupied cyclin D1 and rDNA promoters, enhancing their activity in the presence of v-src.

Conclusions:

  • IRS-2 plays a critical role in v-src-induced oncogenic transformation.
  • Targeting IRS-2 may offer a therapeutic strategy to reverse v-src-driven cancers.

More Related Videos

An Immunofluorescent Method for Characterization of Barrett’s Esophagus Cells08:54

An Immunofluorescent Method for Characterization of Barrett’s Esophagus Cells

Published on: July 20, 2014

Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence10:09

Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence

Published on: January 7, 2019

Related Concept Videos

Insulin: The Receptor and Signaling Pathways01:28

Insulin: The Receptor and Signaling Pathways

Insulin action is mediated through a receptor tyrosine kinase, akin to the IGF-1 receptor. The number of receptors per cell varies significantly, from 40 on erythrocytes to 300,000 on adipocytes and hepatocytes. The insulin receptor consists of linked α/β subunit dimers, forming a heterotetramer glycoprotein with two extracellular α subunits and two β subunits spanning the membrane. The α subunits inhibit the inherent tyrosine kinase activity of the β subunits, but this inhibition is released...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
Rous Sarcoma Virus (RSV) and Cancer01:03

Rous Sarcoma Virus (RSV) and Cancer

Rous Sarcoma virus or RSV was discovered by F. Peyton Rous in the year 1911 as a filterable transmissible agent that could cause tumors in chickens. He won a Nobel Prize for this discovery in 1966. His experiments clearly demonstrated that some cancers could be caused by infectious agents and led to the discovery of many more cancer-causing viruses in animals as well as humans.
RSV is a retrovirus that contains two copies of a plus-strand  RNA genome. Its genome consists of four main open...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...
The Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...