Caveolin-1: a multifaceted driver of breast cancer progression and its application in clinical treatment

Abstract

Human breast cancer is one of the most frequent cancer diseases and causes of death among female population worldwide. It appears at a high incidence and has a high malignancy, mortality, recurrence rate and poor prognosis. Caveolin-1 (Cav1) is the main component of caveolae and participates in various biological events. More and more experimental studies have shown that Cav1 plays a critical role in the progression of breast cancer including cell proliferation, apoptosis, autophagy, invasion, migration and breast cancer metastasis. Besides, Cav1 has been found to be involved in chemotherapeutics and radiotherapy resistance, which are still the principal problems encountered in clinical breast cancer treatment. In addition, stromal Cav1 may be a potential indicator for breast cancer patients' prognosis. In the current review, we cover the state-of-the-art study, development and progress on Cav1 and breast cancer, altogether describing the role of Cav1 in breast cancer progression and application in clinical treatment, in the hope of providing a basis for further research and promoting CAV1 gene as a potential target to diagnose and treat aggressive breast cancers.

Keywords: breast cancer; caveolin-1; invasion; metastasis; migration; prognosis.

Figure 1

The structure of caveolae. Notes: Caveolae are 50–100 nm Ω-shaped, cholesterol-enriched, rigid membrane microdomains that are composed of scaffold proteins named caveolins. The most important constituent protein is Caveolin-1.

Figure 2

Cav1 and breast cancer prognosis. Notes: CAFs and epithelium Cav1 expression may be primary prognostic indicators for breast cancer patients. Loss of CAFs Cav1 expression and high expression levels of epithelium Cav1 often show a poor clinical outcome. Moreover, cytoplasmic EGFR and stromal MCT-4 may be secondary prognostic indicators. Abbreviations: CAFs, cancer-associated fibroblasts; Cav1, caveolin-1; MCT-4, monocarboxylate transporter 4.

Figure 3

Cav1 acts both as a suppressor and a promoter in breast cancer cell tumorigenesis. Notes: Cav1 can act as a suppressor in breast cancer cell carcinogenic process via suppressing breast cancer cell proliferation, autophagy, invasion and migration and promoting apoptosis. Cav1 can also act as a promoter in breast cancer cell carcinogenic process via promoting breast cancer cell proliferation, autophagy, invasion, migration and metastasis, and suppressing apoptosis and anoikis. Abbreviations: BKCa, large conductance Ca²⁺-activated potassium; Cav1, caveolin-1; CSF1, colony-stimulating factor 1; EMT, epithelial to mesenchymal transition; FSP-1, fibroblast-specific protein-1; HER2, human epidermal growth factor receptor-2; HSP90, heat shock protein 90; MMP, matrix metalloproteinase; MT4-MMP, membrane type 4 matrix metalloproteinase; VEGF, vascular endothelial growth factor; SDF-1, stromal cell-derived factor-1.