ArticleOncogene2000
Grb2 downregulation leads to Akt inactivation in heregulin-stimulated and ErbB2-overexpressing breast cancer cells.
Article in Oncogene, 2000. 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, 41 citations in OpenAlex.
- FOXK1 drives colorectal cancer progression by transcriptionally activating GRB2.European journal of medical research · 2025Article
- GRB2 regulation of essential signaling pathways in the endometrium is critical for implantation and decidualization.Nature communications · 2025Article
- DDR1 promotes metastasis of cervical cancer and downstream phosphorylation signal via binding GRB2.Cell death & disease · 2024Article
- Oncoinformatic screening of the gene clusters involved in the HER2-positive breast cancer formation along with the in silico pharmacodynamic profiling of selective long-chain omega-3 fatty acids as the metastatic antagonists.Molecular diversity · 2023Article
- Anticancer effect of zanubrutinib in HER2-positive breast cancer cell lines.Investigational new drugs · 2023Article
- PLAC1 is essential for FGF7/FGFRIIIb-induced Akt-mediated cancer cell proliferation.Oncotarget · 2020Article
- KPNA2-Associated Immune Analyses Highlight the Dysregulation and Prognostic Effects of GRB2, NRAS, and Their RNA-Binding Proteins in Hepatocellular Carcinoma.Frontiers in genetics · 2020Article
- Role of HER2 mutations in refractory metastatic breast cancers: targeted sequencing results in patients with refractory breast cancer.Oncotarget · 2015Article
- MicroRNA 320a functions as a novel endogenous modulator of aquaporins 1 and 4 as well as a potential therapeutic target in cerebral ischemia.The Journal of biological chemistry · 2010Article
- Discovery of thioether-bridged cyclic pentapeptides binding to Grb2-SH2 domain with high affinity.Bioorganic & medicinal chemistry letters · 2009Article
- Grb2-SH3 ligand inhibits the growth of HER2+ cancer cells and has antitumor effects in human cancer xenografts alone and in combination with docetaxel.International journal of cancer · 2007Article
- KGF-induced motility of breast cancer cells is dependent on Grb2 and Erk1,2.Clinical & experimental metastasis · 2004Article
- Growth factor signaling induces metastasis genes in transformed cells: molecular connection between Akt kinase and osteopontin in breast cancer.Molecular and cellular biology · 2003Article
- Blockage of heregulin expression inhibits tumorigenicity and metastasis of breast cancer.Oncogene · 2003Article
- Article
- PKB-mediated negative feedback tightly regulates mitogenic signalling via Gab2.The EMBO journal · 2002Article
- Binding of the cSH3 domain of Grb2 adaptor to two distinct RXXK motifs within Gab1 docker employs differential mechanisms.Journal of molecular recognition : JMRArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
ErbB2 can be activated by its own overexpression or be transactivated by the heregulin polypeptide growth factor. Activation of ErbB2 leads to breast cancer cell proliferation, presumably by inducing the activation of extracellular signal-regulated kinases 1,2 (Erk1,2) and Akt. We have previously reported that the growth factor receptor bound protein-2 (Grb2) is required for the proliferation of ErbB2-overexpressing breast cancer cells. We investigated here whether Grb2 protein plays a role in heregulin-stimulated proliferation. Grb2 protein inhibition led to growth inhibition of heregulin-stimulated breast cancer cells, but not Erk1,2 inactivation. These findings are similar to our earlier observations in ErbB2-overexpressing cells. Since Akt can also be activated by heregulin, the effects of Grb2 inhibition on Akt were examined. Akt was inactivated following Grb2 downregulation in heregulin-stimulated breast cancer cells. We then examined the effects of Grb2 downregulation on Akt in ErbB2-overexpressing cells in the absence of heregulin. Similar to heregulin-stimulated cells, Grb2 inhibition also led to Akt inactivation in ErbB2-overexpressing breast cancer cells. Our results indicate that the activation of ErbB2 by heregulin or by its overexpression requires Grb2 to stimulate the Akt pathway to propagate mitogenic signals.
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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 OpenQuestion graph.