p130Cas alters the differentiation potential of mammary luminal progenitors by deregulating c-Kit activity.
Giusy Tornillo,Angela Rita Elia,Isabella Castellano,Michela Spadaro,Paola Bernabei,Brigitte Bisaro,Maria del Pilar Camacho-Leal,Alessandra Pincini,Paolo Provero,Anna Sapino,Emilia Turco,Paola Defilippi,Sara Cabodi +12 more
TLDR
High levels of p130Cas, via abnormal c‐Kit activation, promote mammary luminal cell plasticity, thus providing the conditions for the development of basal‐like breast cancer.Abstract:
It has recently been proposed that defective differentiation of mammary luminal progenitors predisposes to basal-like breast cancer. However, the molecular and cellular mechanisms involved are still unclear. Here, we describe that the adaptor protein p130Cas is a crucial regulator of mouse mammary epithelial cell (MMEC) differentiation. Using a transgenic mouse model, we show that forced p130Cas overexpression in the luminal progenitor cell compartment results in the expansion of luminal cells, which aberrantly display basal cell features and reduced differentiation in response to lactogenic stimuli. Interestingly, MMECs overexpressing p130Cas exhibit hyperactivation of the tyrosine kinase receptor c-Kit. In addition, we demonstrate that the constitutive c-Kit activation alone mimics p130Cas overexpression, whereas c-Kit downregulation is sufficient to re-establish proper differentiation of p130Cas overexpressing cells. Overall, our data indicate that high levels of p130Cas, via abnormal c-Kit activation, promote mammary luminal cell plasticity, thus providing the conditions for the development of basal-like breast cancer. Consistently, p130Cas is overexpressed in human triple-negative breast cancer, further suggesting that p130Cas upregulation may be a priming event for the onset of basal-like breast cancer.read more
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p130Cas/BCAR1 scaffold protein in tissue homeostasis and pathogenesis.
Maria del Pilar Camacho Leal,Marianna Sciortino,Giusy Tornillo,Shana Colombo,Paola Defilippi,Sara Cabodi +5 more
TL;DR: More recent data on the contribution of p130Cas/BCAR1 in the regulation of tissue homeostasis and its potential implications in pathological conditions are discussed.
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Cas proteins: dodgy scaffolding in breast cancer
TL;DR: Two Cas proteins are focused on, p130Cas/BCAR1 and Nedd9, and their coupled signalling pathways, to examine their role in mammary cell transformation and in the acquirement of invasiveness and drug resistance of breast cancer cells.
Journal ArticleDOI
Association of the breast cancer antiestrogen resistance protein 1 (BCAR1) and BCAR3 scaffolding proteins in cell signaling and antiestrogen resistance.
TL;DR: It is shown that BCAR3-induced antiestrogen resistance in MCF7 breast cancer cells critically depends on its ability to bind BCAR1, and strategies to disruptBCAR1-BCAR3/NSP3 complexes and associated signaling networks could ultimately lead to new breast cancer therapies.
Journal ArticleDOI
Essential role of SH3GL1 in interleukin-6(IL-6)- and vascular endothelial growth factor (VEGF)-triggered p130 cas -mediated proliferation and migration of osteosarcoma cells
En-qi Li,Jin-li Zhang +1 more
TL;DR: The results strongly suggest that SH3GL1 is a novel target for anti-osteosarcoma.
Journal ArticleDOI
Identification of afzelin potential targets in inhibiting triple-negative breast cancer cell migration using reverse docking.
TL;DR: Afzelin was predicted to inhibit TNBC cell motility, by targeting ERK2, KRas, and FAK activation and played a dominant role in forming hydrogen bonds with the target proteins.
References
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Aberrant luminal progenitors as the candidate target population for basal tumor development in BRCA1 mutation carriers
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