Year: 2014
Type: dissertation
Abstract: Increasing evidence indicates the importance of the tumor microenvironment in cancer progression. Cancer-associated fibroblasts (CAFs), in particular, have been reported to support tumorigenesis by promoting cell proliferation, invasion and angiogenesis. However, the mechanisms by which CAFs and tumor cells, specifically the basal-like subtype of breast cancer (BLBC), interact with each other, remain unclear. Interestingly, BLBC tumors are characterized by activation of the Notch pathway. Here, we performed co-cultures of BLBC cells with CAF-like fibroblasts and investigated the role of Notch in these interactions. We showed CAF-derived TGFb drives tumor Notch signaling and expression of the Notch target uPA. Notch activation also drives expression of c-MET which is required for uPA expression. Supporting functional assays suggested CAF-like cells promote invasion of MDA-MB231, in a fashion that depends upon TGFbR1, c-MET, uPA and Notch. Therefore, Notch participates in tumor-CAF crosstalk in BLBC cells, and may represent an important target for cancer therapy.
Source: TSpace (University of Toronto)
Author: Jifeng Song
Language: English
Topic: TGF-β signaling in diseases
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2624922532