Caveolae/Caveolin-1 Are Important Modulators of Store-Operated Calcium Entry in Hs578/T Breast Cancer Cells

Abstract

Abstract. Caveolin-1 is a principal component of caveolae, invaginations of the plasma membrane that are enriched in cholesterol and sphingolipids. The expression of caveolin-1 has been shown to be tightly correlated to the progression of breast cancer tumors. However, the consequences of altered caveolin-1 expression during tumor progression still remain unclear. Modification of caveolin-1 expression modulates store-operated Ca 2+ entry (SOCE) in various cell types. SOCE is a ubiquitous Ca 2+ entry pathway that previous studies have linked to apoptosis and tumor progression in prostate cancer cells. In this study, we tested the effect of altering caveolin-1 expression on SOCE in Hs578/ T breast cancer cells. Through overexpression of caveolin-1 and small hairpin RNA (shRNA) knockdown, we generated four stable cell lines that have 3 different caveolin-1 protein levels. Cav-1 overexpression could increase SOCE activity, while knockdown of caveolin-1 significantly reduced SOCE activity. These functional consequences were correlated with changes in caveolae number in Hs578/ T cells. Our results suggest alteration of SOCE by caveolin-1 expression changes could be one of the mechanisms contributing to the progression of breast cancer.

STIM1/ORAI1-mediated Ca2+ Influx Regulates Enolase-1 Exteriorization

“…A growing body of evidence suggests that elevated expression of cav-1 in advanced stages of cancer promotes tumor cell proliferation and spreading (52,53). This phenomenon can be partially explained by cav-1-dependent stimulation of store operated Ca 2ϩ entry (SOCE) and thus activation of multiple signaling pathways (54), which in turn may initiate cav-1 expression (55), thereby creating a positive feedback loop. In view of these results, it is tempting to speculate that altered levels of intracellular Ca 2ϩ not only affect expression of cav-1 but also facilitate its binding to ENO-1 and thus the transport of this glycolytic enzyme to the cell surface, finally leading to increased pericellular proteolytic activity and thus cell spreading.…”

Plasma Membrane-associated Annexin A6 Reduces Ca2+ Entry by Stabilizing the Cortical Actin Cytoskeleton

“…Many details of SOCE, including the functional STIM-Orai1 protein complex remain to be elucidated. Caveolae have been suggested as important Ca 2ϩ entry sites, and recently it has been shown that alterations of caveolin expression modulated SOCE (52). Likewise, it has been reported that the disruption of cholesterol-rich microdomains reduces Ca 2ϩ entry (53).…”

β-Dystroglycan binds caveolin-1 in smooth muscle: a functional role in caveolae distribution and Ca2+ release

“…Collectively, these results support a role for the actin cytoskeleton, through its tethering to a DGC-caveolin-1 complex, in the establishment and maintenance of discrete caveolae microdomains in smooth muscle cells. release in the smooth muscle and other cell systems (Daniel et al, 2009;Darby et al, 2000;El-Yazbi et al, 2008;Gosens et al, 2007b;Prakash et al, 2007;Sengupta et al, 2008;Zhu et al, 2008). We assessed whether this functional role is linked to the unique ordered distribution of caveolae in contractile smooth muscle cells.…”