ArticleThe Journal of biological chemistry2013
Distinct phosphotyrosine-dependent functions of the ShcA adaptor protein are required for transforming growth factor β (TGFβ)-induced breast cancer cell migration, invasion, and metastasis.
Article in The Journal of biological chemistry, 2013. 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, 19 citations in OpenAlex.
- The SHCA adapter protein cooperates with lipoma-preferred partner in the regulation of adhesion dynamics and invadopodia formation.The Journal of biological chemistry · 2020Article
- p66ShcA functions as a contextual promoter of breast cancer metastasis.Breast cancer research : BCR · 2020Article
- Cyanobacterial bioactive compound EMTAHDCA recovers splenomegaly, affects protein profile of E. coli and spleen of lymphoma bearing mice.Molecular biology reports · 2019Article
- Down-regulation of HOXB5 inhibits TGF-β-induced migration and invasion in hepatocellular carcinoma cellsRSC advances · 2018Article
- Emerging roles for LPP in metastatic cancer progression.Journal of cell communication and signaling · 2018Review
- LPP is a Src substrate required for invadopodia formation and efficient breast cancer lung metastasis.Nature communications · 2017Article
- Agonists and knockdown of estrogen receptor β differentially affect invasion of triple-negative breast cancer cells in vitro.BMC cancer · 2016Article
- Up-regulation of N-cadherin by Collagen I-activated Discoidin Domain Receptor 1 in Pancreatic Cancer Requires the Adaptor Molecule Shc1.The Journal of biological chemistry · 2016Article
- Chordin-Like 1 Suppresses Bone Morphogenetic Protein 4-Induced Breast Cancer Cell Migration and Invasion.Molecular and cellular biology · 2016Article
- Targeting metastasis.Nature reviews. Cancer · 2016Review
- GPNMB cooperates with neuropilin-1 to promote mammary tumor growth and engages integrin α5β1 for efficient breast cancer metastasis.Oncogene · 2015Article
- High serum transforming growth factor beta 1 (TGFB1) level predicts better survival in breast cancer.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014Article
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7 authors at 3 institutions in 2 countries.
Funding
Abstract
The ErbB2 and TGFβ signaling pathways cooperate to promote the migratory, invasive, and metastatic behavior of breast cancer cells. We previously demonstrated that ShcA is necessary for these synergistic interactions. Through a structure/function approach, we now show that the phosphotyrosine-binding, but not the Src homology 2, domain of ShcA is required for TGFβ-induced migration and invasion of ErbB2-expressing breast cancer cells. We further demonstrate that the tyrosine phosphorylation sites within ShcA (Tyr(239)/Tyr(240) and Tyr(313)) transduce distinct and non-redundant signals that promote these TGFβ-mediated effects. We demonstrate that Grb2 is required specifically downstream of Tyr(313), whereas the Tyr(239)/Tyr(240) phosphorylation sites require the Crk adaptor proteins to augment TGFβ-induced migration and invasion. Furthermore, ShcA Tyr(313) phosphorylation enhances tumor cell survival, and ShcA Tyr(239)/Tyr(240) signaling promotes endothelial cell recruitment into ErbB2-expressing breast tumors in vivo, whereas all three ShcA tyrosine residues are required for efficient breast cancer metastasis to the lungs. Our data uncover a novel ShcA-dependent signaling axis downstream of TGFβ and ErbB2 that requires both the Grb2 and Crk adaptor proteins to increase the migratory and invasive properties of breast cancer cells. In addition, signaling downstream of specific ShcA tyrosine residues facilitates the survival, vascularization, and metastatic spread of breast tumors.
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