ArticleThe Journal of biological chemistry2017
Differential involvement of the microtubule cytoskeleton in insulin receptor substrate 1 (IRS-1) and IRS-2 signaling to AKT determines the response to microtubule disruption in breast carcinoma cells.
Article in The Journal of biological chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 24 citations in OpenAlex.
- The Role of Runx2 in Microtubule Dynamics and Its Effects on Osteoblast Migration.Cytoskeleton (Hoboken, N.J.) · 2026Article
- Interaction of IRS2 with PLK1 protects cells from mitotic stress.Cell death & disease · 2026Article
- Role of the PI3K/AKT signaling pathway in the cellular response to Tumor Treating Fields (TTFields).Cell death & disease · 2025Article
- Inhibition of LAR attenuates neuroinflammation through RhoA/IRS-1/Akt signaling pathway after intracerebral hemorrhage in mice.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2023Article
- miR-33a Inhibits the Differentiation of Bovine Preadipocytes through the IRS2-Akt Pathway.Genes · 2023Article
- Suppression of Insulin Receptor Substrate 1 Inhibits Breast Cancer Growth In Vitro and in Female Athymic Mice.Endocrinology · 2023Article
- Article
- Review
- Diversity of insulin and IGF signaling in breast cancer: Implications for therapy.Molecular and cellular endocrinology · 2021Review
- Insulin receptor substrate-1 (IRS-1) mediates progesterone receptor-driven stemness and endocrine resistance in oestrogen receptor+ breast cancer.British journal of cancer · 2021Article
- Insulin Receptor Substrate Suppression by the Tyrphostin NT157 Inhibits Responses to Insulin-Like Growth Factor-I and Insulin in Breast Cancer Cells.Hormones & cancer · 2018Article
- Scinderin-knockdown inhibits proliferation and promotes apoptosis in human breast carcinoma cells.Oncology letters · 2018Article
- Identification of a Novel Invasion-Promoting Region in Insulin Receptor Substrate 2.Molecular and cellular biology · 2018Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The insulin receptor substrate (IRS) proteins serve as essential signaling intermediates for the activation of PI3K by both the insulin-like growth factor 1 receptor (IGF-1R) and its close family member, the insulin receptor (IR). Although IRS-1 and IRS-2 share significant homology, they regulate distinct cellular responses downstream of these receptors and play divergent roles in breast cancer. To investigate the mechanism by which signaling through IRS-1 and IRS-2 results in differential outcomes, we assessed the involvement of the microtubule cytoskeleton in IRS-dependent signaling. Treatment with drugs that either stabilize or disrupt microtubules reveal that an intact microtubule cytoskeleton contributes to IRS-2- but not IRS-1-mediated activation of AKT by IGF-1. Proximal IGF-1R signaling events, including IRS tyrosine phosphorylation and recruitment of PI3K, are not inhibited by microtubule disruption, indicating that IRS-2 requires the microtubule cytoskeleton at the level of downstream effector activation. IRS-2 colocalization with tubulin is enhanced upon Taxol-mediated microtubule stabilization, which, together with the signaling data, suggests that the microtubule cytoskeleton may facilitate access of IRS-2 to downstream effectors such as AKT. Of clinical relevance is that our data reveal that expression of IRS-2 sensitizes breast carcinoma cells to apoptosis in response to treatment with microtubule-disrupting drugs, identifying IRS-2 as a potential biomarker for the response of breast cancer patients to
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