Cell Biology and Translational Medicine, Volume 20 by Unknown

Author:Unknown
Language: eng
Format: epub
ISBN: 9783031416880
Publisher: Springer Nature Switzerland

11 Caveolae in Cancer

Caveolar composition and signaling have long been related to cancer. First, it was observed that Cav1 levels decreased and caveolae got lost during the cellular transformation of NIH 3T3 cells after the expression of oncogenes (Koleske et al. 1995). Cav1 expression levels are inversely correlated with the colony size of the transformed cells (Koleske et al. 1995). Also, Cav1 knock-out mice exhibit hyperproliferation in the lung and vascular tissues (Drab et al. 2001; Razani et al. 2001). Next, a role for Cav1 in breast cancer is described. Cav1 deletion in MMTV-PyMT model of breast cancer in mice leads to a delayed initiation of tumor growth, an increase in tumor burden, ERK1 hyperactivation, and cyclinD1 overexpression (Williams et al. 2004). However, cancer progression and survival studies revealed that the main predictor of survival is the Cav1 level in stromal cells rather than epithelia (Sloan et al. 2009; Witkiewicz et al. 2009). The lower the expression of Cav1 in stromal cells, the faster the cancer progresses (Sloan et al. 2009; Witkiewicz et al. 2009). Lisanti and colleagues isolated breast stromal cells (cancer-associating fibroblasts (CAFs)) from patients and compared their metabolism to normal fibroblasts of the matched patient (Martinez-Outschoorn et al. 2015; Pavlides et al. 2009). CAFs represent significant metabolic/expressional differences compared to normal fibroblasts. Then, they devise a physiological mechanism named the “Reverse Warburg Effect” in which transformed cells induce a differentiation program in stromal cells (Martinez-Outschoorn et al. 2015; Pavlides et al. 2009) Therefore, the idea is that cancer cells induce tumor stromal cells to undergo a myofibroblast differentiation. Differentiated tumor stroma activates TGFβ signaling and goes through a metabolic transformation yielding a Warburg metabolism in stromal cells, although present in normoxic conditions. Metabolically altered stroma then sustains the tumor growth and progression by representing metabolites like lactate or pyruvate (Pavlides et al. 2009). Besides Cav1, caveolar protein cavin1 is considered a prognostic marker for prostate cancer (Moon et al. 2014b), while caveolar CD36 protein level is associated with breast cancer (DeFilippis et al. 2012).

Download

Copyright Disclaimer:
This site does not store any files on its server. We only index and link to content provided by other sites. Please contact the content providers to delete copyright contents if any and email us, we'll remove relevant links or contents immediately.