2009
DOI: 10.1074/jbc.m109.023614
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p130Cas Is Required for Mammary Tumor Growth and Transforming Growth Factor-β-mediated Metastasis through Regulation of Smad2/3 Activity

Abstract: During breast cancer progression, transforming growth factor-␤ (TGF-␤) switches from a tumor suppressor to a prometastatic molecule. Several recent studies suggest that this conversion in TGF-␤ function depends upon fundamental changes in the TGF-␤ signaling system. We show here that these changes in TGF-␤ signaling are concomitant with aberrant expression of the focal adhesion protein, p130Cas. Indeed, elevating expression of either the full-length (FL) or just the carboxyl terminus (CT) of p130Cas in mammary… Show more

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Cited by 69 publications
(108 citation statements)
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“…As a consequence, the transcription of the cyclin-dependent kinase inhibitors p15 and p21 is inhibited, resulting in cell cycle progression 72 . Recently, it has been reported that p130CAS over-expression in mammary epithelial cells (MECs) shifts TGF signalling from SMAD2/SMAD3 phosphorylation to p38 MAPK activation, rendering MECs resistant to TGF-induced growth arrest and enhancing their metastatic potential 73 . Notably, NEDD9 was found to be a new transcriptional target of TGF signalling in highly metastatic mammary adenocarcinoma cells that switch from collective motility to single cell motility, and its silencing results in inhibition of amoeboid motility in response to TGF 74 .…”
Section: Migration and Invasionmentioning
confidence: 99%
“…As a consequence, the transcription of the cyclin-dependent kinase inhibitors p15 and p21 is inhibited, resulting in cell cycle progression 72 . Recently, it has been reported that p130CAS over-expression in mammary epithelial cells (MECs) shifts TGF signalling from SMAD2/SMAD3 phosphorylation to p38 MAPK activation, rendering MECs resistant to TGF-induced growth arrest and enhancing their metastatic potential 73 . Notably, NEDD9 was found to be a new transcriptional target of TGF signalling in highly metastatic mammary adenocarcinoma cells that switch from collective motility to single cell motility, and its silencing results in inhibition of amoeboid motility in response to TGF 74 .…”
Section: Migration and Invasionmentioning
confidence: 99%
“…[40][41][42] Later studies revealed that BCAR1 plays an essential role in cell transformation by SRC and several other oncogenes. 37,[43][44][45][46][47][48] The human gene was identified in a genome-wide screen for proteins whose overexpression in estrogen-dependent breast cancer cells confers resistance to antiestrogens (hence, the name breast cancer antiestrogen resistance protein 1, abbreviated to BCAR1) ( Table 1). [49][50][51] BCAR1 has also been implicated in resistance to the chemotherapeutic drug doxorubicin.…”
Section: Bcar1 (P130cas)mentioning
confidence: 99%
“…Delivery of p130 Cas /BCAR1-specific siRNAs into the mammary gland of transgenic BALB-HER2/neu mice carrying the activated HER2/neu oncogene was sufficient to inhibit HER2/neu signaling and decreased the growth of spontaneous tumors in vivo (Cabodi et al 2010b). The balance between canonical and noncanonical transforming growth factor (TGF)- signaling in mammary carcinomas is also regulated by p130 Cas (Wendt et al 2009). Maintaining this balance is critical as TGF- acts as both a tumor-suppressor or tumorpromoter depending on the tumor microenvironment and tumor stage (as reviewed in Ikushima & Miyazono 2010;Meulmeester & Ten Dijke 2011).…”
Section: Involvement Of Cas Family Members In Mammary Carcinomasmentioning
confidence: 99%
“…Maintaining this balance is critical as TGF- acts as both a tumor-suppressor or tumorpromoter depending on the tumor microenvironment and tumor stage (as reviewed in Ikushima & Miyazono 2010;Meulmeester & Ten Dijke 2011). Forced expression of either full length p130 Cas or the CTD of p130 Cas in mammary epithelial cells (MECs) shifted TGF- signaling from Smad2/3 to p38 MAPK activation resulting in resistance of TGF--induced growth arrest and increased invasion and metastasis of MECs in vivo utilizing an orthotopic mouse model (Wendt et al 2009). In addition to p130 Cas , HEF1, also mediates TGF- tumor promoting activities.…”
Section: Involvement Of Cas Family Members In Mammary Carcinomasmentioning
confidence: 99%