ArticleMolecular biology of the cell2011
Gab2 regulates cytoskeletal organization and migration of mammary epithelial cells by modulating RhoA activation.
Article in Molecular biology of the cell, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 25 citations in OpenAlex.
- DLK1-DIO3 region as a source of tumor suppressor miRNAs in papillary thyroid carcinoma.Translational oncology · 2024Article
- An analysis of the role of GAB2 in pan-cancer from a multidimensional perspective.Discover oncology · 2024Article
- Article
- Targeting promiscuous heterodimerization overcomes innate resistance to ERBB2 dimerization inhibitors in breast cancer.Breast cancer research : BCR · 2019Article
- BRAF inhibition upregulates a variety of receptor tyrosine kinases and their downstream effector Gab2 in colorectal cancer cell lines.Oncogene · 2018Article
- Gab2 mediates hepatocellular carcinogenesis by integrating multiple signaling pathways.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2017Article
- Diatrack particle tracking software: Review of applications and performance evaluation.Traffic (Copenhagen, Denmark) · 2017Review
- Gab2 facilitates epithelial-to-mesenchymal transition via the MEK/ERK/MMP signaling in colorectal cancer.Journal of experimental & clinical cancer research : CR · 2016Article
- Structure and function of Gab2 and its role in cancer (Review).Molecular medicine reports · 2015Review
- Wnt4 inhibits cell motility induced by oncogenic Ras.Oncogene · 2013Article
- Alterations of Gab2 signalling complexes in imatinib and dasatinib treated chronic myeloid leukaemia cells.Cell communication and signaling : CCS · 2013Article
- Gab2 phosphorylation by RSK inhibits Shp2 recruitment and cell motility.Molecular and cellular biology · 2013Article
- Bringing balance by force: live cell extrusion controls epithelial cell numbers.Trends in cell biology · 2013Review
- Gab2 signaling in chronic myeloid leukemia cells confers resistance to multiple Bcr-Abl inhibitors.Leukemia · 2013Article
- GAB2--a scaffolding protein in cancer.Molecular cancer research : MCR · 2012Review
- Gab2 regulates the migratory behaviors and E-cadherin expression via activation of the PI3K pathway in ovarian cancer cells.Oncogene · 2012Article
- Gab adapter proteins as therapeutic targets for hematologic disease.Advances in hematology · 2012Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The docking protein Gab2 is overexpressed in several human malignancies, including breast cancer, and is associated with increased metastatic potential. Here we report that Gab2 overexpression in MCF-10A mammary epithelial cells led to delayed cell spreading, a decrease in stress fibers and mature focal adhesions, and enhanced cell migration. Expression of a Gab2 mutant uncoupled from 14-3-3-mediated negative feedback (Gab2(2xA)) led to a more mesenchymal morphology and acquisition of invasive potential. Expression of either Gab2 or Gab2(2xA) led to decreased activation of RhoA, but only the latter increased levels of Rac-GTP. Expression of constitutively active RhoA in MCF-10A/Gab2 cells restored stress fibers and focal adhesions, indicating that Gab2 signals upstream of RhoA to suppress these structures. Mutation of the two Shp2-binding sites to phenylalanine (Gab2(ΔShp2)) markedly reduced the effects of Gab2 on cellular phenotype and RhoA activation. Expression of Gab2 or Gab2(2xA), but not Gab2(ΔShp2), promoted Vav2 phosphorylation and plasma membrane recruitment of p190A RhoGAP. Knockdown of p190A RhoGAP reversed Gab2-mediated effects on stress fibers and focal adhesions. The identification of a novel pathway downstream of Gab2 involving negative regulation of RhoA by p190A RhoGAP sheds new light on the role of Gab2 in cancer progression.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.