The ShcA adaptor protein is a critical regulator of breast cancer progression.
Breast cancer affects 1 in 8 North American women throughout their lifetime and is the second leading cause of cancer-related deaths. Breast cancer is a heterogeneous disease whose progression from hyperplasia to ductal carcinoma in situ and invasive carcinoma is regulated by the aberrant expression of multiple mediators; including growth factors, cytokines, chemokines and proteases that are produced both by the mammary tumor itself and the adjacent reactive stroma. These signals promote tumor cell proliferation, survival, establishment of a tumor vasculature, invasion and ultimately metastasis to secondary organs. Moreover, the ability of the tumor to create a state of local immune suppression allows tumor cells to evade clearance by the immune system. ShcA is an adaptor protein that relays extracellular signals downstream of receptor tyrosine kinases. Clinical studies suggest that activation of the ShcA signaling pathway is associated with poor patient prognosis. Moreover, recent studies with transgenic mouse models have clearly demonstrated the importance of tumor autonomous ShcA signaling, as well as signaling in cells comprising the tumor microenvironment, for the regulation of these biological processes, which contribute to breast cancer development and metastasis.
Ursini-Siegel
Josie
J
Department of Medicine, McGill University, Montreal, Quebec, Canada.
Muller
William J
WJ
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002465:Cell Movement; D049109:Cell Proliferation; D018450:Disease Progression; D005260:Female; D051380:GRB2 Adaptor Protein / Q000378:metabolism*; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology; D055765:Shc Signaling Adaptor Proteins; D015398:Signal Transduction; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1
D048868:Adaptor Proteins, Signal Transducing; C413364:ERBIN protein, human; D051380:GRB2 Adaptor Protein; D016023:Integrins; C528024:SHC1 protein, human; D055765:Shc Signaling Adaptor Proteins; C528034:Shc1 protein, mouse; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1