Caveolin-1 Modulates Docetaxel-Induced Cell Death in Breast Cancer Cell Subtypes through Different Mechanisms

Abstract

PurposeCaveolin-1 (CAV-1) expression is more associated with basal-like cancers than estrogen receptor- or ErbB-2–expressing breast cancers. However, the biological relevance of different levels of CAV-1 expression according to subtype in the epithelial compartment of breast cancer remains unclear.Materials and MethodsWe investigated whether CAV-1 functions as a tumor suppressor and/or modulator of the cytotoxic activity of docetaxel (DTX) in subtypes of breast cancer using in vitro and xenograft models.ResultsThe levels of CAV-1 expression were closely associated with DTX sensitivity in triple-negative breast cancer cells. In addition, CAV-1 significantly inhibited cell proliferation and modulated DTX-induced apoptosis through cell cycle arrest in the G2/M phase. The mechanisms underlying DTX-induced apoptosis differed in breast cancers according to the levels of CAV-1 expression. DTX robustly enhanced Bcl-2 inactivation by CAV-1 in MDA-MB-231 cells, while p53-mediated cell cycle arrest by DTX was more pronounced in CAV-1–low but p53-functional MCF-7 cells. In parallel with the data from breast cancer cell lines, CAV-1–transfected MCF-7 cells showed higher efficacy of DTX treatment in a xenograft model.ConclusionWe clearly demonstrated cooperative effects between CAV-1 and DTX in mediating apoptosis, suggesting that the levels of CAV-1 expression might be an important indicator for DTX use in breast cancer.

Docetaxel-loaded solid lipid nanoparticles prevent tumor growth and lung metastasis of 4T1 murine mammary carcinoma cells

“…The in vivo therapeutic performances of SLN-DTX and free DTX were studied in 4T1 tumor-bearing Balb/c mice at 10 mg/kg DTX for a total of five doses. The dose was selected based on the previous works in literature [8,44,65]. In agreement with the in vitro cytotoxicity data, the group treated with SLN-DTX showed the lowest tumor growth rate (Fig.…”

Impact of the hypoxic phenotype on the uptake and efflux of nanoparticles by human breast cancer cells

“…Further, the recycling of transmembrane proteins may also be influenced by interaction with proteins like Caveolin 1, among others 64 . Interestingly, constitutive in vitro expression of Caveolin 1 is markedly higher in MDA-MB-231 cells than in many other tumor cell lines 65 , 66 , suggesting its potential for a greater influence in this cell line. Similarly, upregulation of exocytotic release of exosomes or vesicles from tumor cells during hypoxia is known to play a significant role in tumor development and signaling 37 , 67 , with implications for altered or upregulated exocytosis.…”

Missing-in-metastasis B (MIM-B) combined with caveolin-1 promotes metastasis of hepatocellular carcinoma

“…Caveolin-1, a 21–24-kDa membrane protein, is a member of the caveolin family of proteins and is also the main structural component of caveolae [ 23 – 25 ]. Caveolin-1 plays key roles in several cellular processes, such as caveolae-mediated vesicular transport and endocytosis, lipid metabolism, cell adhesion, cell migration, cell signaling platform regulation, cell transformation, cell proliferation, cell cycle arrest, anchorage-independent growth and apoptotic cell death [ 26 , 27 ]. Recent reports showed that caveolin-1 is a candidate tumor suppressor gene and participates in the pathogenesis of oncogenic cell transformation and tumorigenesis.…”

“…Recent reports showed that caveolin-1 is a candidate tumor suppressor gene and participates in the pathogenesis of oncogenic cell transformation and tumorigenesis. Moreover, several reports have documented that caveolin-1 expression is altered in various cancers, such as bladder, ovarian, thyroid follicular, breast, esophageal, lung, colon, cervical, and renal cancer; T cell leukemia; and HCC [ 25 , 27 – 31 ]. Notably, caveolin-1 has different functions in variety of cancers and may act both as a tumor suppressor and as a tumor-promoting gene.…”