Up-Regulated Caveolin-1 Accentuates the Metastasis Capability of Lung Adenocarcinoma by Inducing Filopodia Formation

Abstract

Caveolin-1, a 21-to 24-kd protein, is the principal component of caveolae, which are special invaginated microdomains of the plasma membrane present in most mammalian cells. 1 It is well established that caveolin-1 is a tumor suppressor gene. Caveolin-1 mRNA and protein expression are frequently lost in human cancer cell lines. Re-expression of caveolin-1 in oncogenically transformed cell lines inhibits tumor cell growth and reduces tumorigenicity. [2][3][4][5][6] Several mechanisms have been proposed for caveolin-1 to function as a tumor suppressor. Caveolin-1 may exert its tumor-growth inhibition by contact inactivation of signaling molecules such as v-src, Ha-Ras, protein kinase A, PKC, and p42/44 MAP kinase within caveolae. [7][8][9][10] In addition, down-regulation of caveolin-1 in colon carcinoma cells has been shown to prevent the degradation of inducible nitric oxide synthase via the proteosome pathway, which, in turn, increases the local nitric oxide concentration to facilitate tumorigenesis. 11 Caveolin-1 can also function as a tumor metastasispromoting molecule, which is unrelated to its obvious function of cell growth inhibition. 12 Elevated expression of caveolin-1 is found to be associated with progression of prostate, colon, and breast carcinoma. 13,14 Inhibition of c-myc-induced apoptosis by caveolin-1 was recently proposed to promote progression of prostate cancer, 15 and it may serve as a prognostic indicator for these patients. 16 Nonetheless, it still remains unclear whether and how caveolin-1 can potentiate tumor progression in other types of human cancer.In the present study, we investigated the expression pattern of caveolin-1 both in a series of lung carcinoma cell lines (CLs) with varying invasive/metastatic ability 17

AP-1 complexes containing cJun and JunB cause cellular transformation of Rat1a fibroblasts and share transcriptional targets

“…Conflicting evidence exists for the role of caveolin-1 in anchorage-independent growth and invasion. While caveolin-1 inhibits anchorage-independent growth and invasion in 3T3 and MCF-7 breast cancer cells (Engelman et al, 1997;Fiucci et al, 2002), it increases the metastasis of lung adenocarcinoma (Ho et al, 2002) and esophageal carcinoma (Kato et al, 2002). This apparent contradiction may be related to its function as an inhibitor of apoptosis (Timme et al, 2000) and a promoter of survival/clonal growth and metastasis of prostate cancer cells (Li et al, 2001).…”

The emerging role of the PI3-K-Akt pathway in prostate cancer progression

“…21,25,26 Previously, we and others found that expression of caveolin-1 (cav-1), the major component of caveolae, is elevated in prostate cancer and other malignancies. [27][28][29][30][31][32][33][34][35][36][37][38][39][40] To address the molecular mechanism of cav-1-mediated cell survival, we explored a possible link between cav-1 overexpression and Akt activation in prostate cancer cells. When we compared PI3-K-Akt signaling activities in cav-1-expressing LNCaP cells that had undergone adenoviral vector-mediated cav-1 gene transduction with PI3-K-Akt signaling activities in cav-1-negative vector control LNCaP cells, we found that Akt, but not PI3-K activities, were significantly higher in the former.…”

Caveolin-1 inhibits breast cancer growth and metastasis

“…In prostate, esophageal squamous cell carcinoma and lung carcinoma, expression of caveolin-1 correlates with increased metastasis and poor prognosis Li et al, 2001;Ho et al, 2002;Kato et al, 2002). In contrast, caveolin-1 is expressed in normal and benign ovarian epithelial cells and in normal colon mucosa, but is lost in serous ovarian carcinomas (Wiechen et al, 2001) and in colon carcinomas (Bender et al, 2000).…”