Caveolin‑1 and dynamin‑2 overexpression is associated with the progression of bladder cancer

Abstract

Caveolae-mediated endocytosis regulates cell adhesion and growth in an anchorage-dependent manner. Studies of the endocytic function of caveolae have suggested a wide-ranging list of cargoes, including a number of receptors and extracellular proteins, ligands and nutrients from the extracellular matrix. Disruption of the processes of caveolae-mediated endocytosis mediated by signaling proteins is critical to cellular integrity. Caveolin-1 and dynamin-2 are the 2 major proteins associated with endocytotic function. Mechanistically, dynamin-2 has a co-equal role with caveolin-1 in terms of caveolae-derived endosome formation. Recent studies have revealed the pathological outcomes associated with the dysregulation of caveolin-1 and dynamin-2 expression. Increased expression levels of the gene for caveolin, Cav-1, resulting in augmented cellular metastasis and invasion, have been demonstrated in various types of cancer, and overexpression of the gene for dynamin-2, DNM2, has been associated with tumorigenesis in cervical, pancreatic and lung cancer. An increased expression of Cav-1 and DNM2 is known to be associated with the invasive behavior of cancer cells, and with cancer progression. Furthermore, it has been previously demonstrated that, in caveolar assembly and caveolae mediated endocytosis, Cav-1 interacts directly with DNM2 during the processes. Altered expression of the 2 genes is critical for the normal function of the cell. The expression patterns of Cav-1 and DNM2 have been previously examined in bladder cancer cell lines, and were each demonstrated to be overexpressed. In the present study, the expression levels of these 2 genes in bladder cancer samples were quantified. The gene expression levels of Cav-1 and DNM2 were identified to be increased 8.88-and 8.62-fold, respectively, in tumors compared with the normal controls. Furthermore, high-grade tumors exhibited significantly increased expression levels of Cav-1 and DNM2 (both P<0.0001) compared with the low-grade tumors. In addition, compared with normal control samples, the expression of the 2 genes in tumor samples was observed to be highly significant (P<0.0001), with a marked positive correlation identified for the tumors (Pearson's correlation coefficient, r=0.80 for the tumor samples vs. r=0.32 in the normal control samples). Taken together, the results of the present study demonstrated that the overexpression of Cav-1 and DNM2 genes, and a determination of their correlation coefficients, may be a potential risk factor for bladder cancer, in addition to other clinical factors.

Deciphering the Methylation Landscape in Breast Cancer: Diagnostic and Prognostic Biosignatures through Automated Machine Learning

“…DNM2 is known for its role in endocytic cell trafficking and microtubule dynamics. High DNM2 expression is reported in bladder cancer [ 46 ], whereas Chernikova et al showed that levels of DNM2 could predict chemotherapy outcomes for triple-negative BrCa patients [ 47 ]. Another gene included in the signatures and found to be hypermethylated in early BrCa, SSH1 , has been presented to be a cancer progression factor [ 48 ].…”

Association of Caveolin-1 Expression With Prostate Cancer: A Systematic Review and Meta-Analysis

“…Earlier studies indicated that caveolin-1 was related to endocytosis, signaling and lipid disorders, while recent studies focused on clarifying its relevance in cancer. Caveolin-1 is expressed in esophageal carcinoma ( 19 , 20 ), prostate cancer ( 8 – 17 ), colon cancer ( 21 ), breast cancer ( 22 ), bladder cancer ( 23 ), lung cancer ( 24 ), and other cancers ( 25 , 26 ), and acts as a tumor promoter or suppressor. As a tumor promoter, high expression of caveolin-1 drives tumorigenesis by inhibiting apoptosis, facilitating anchorage-independent growth, drug resistance as well as metastasis ( 27 , 28 ).…”

Caveolin-1 function at the plasma membrane and in intracellular compartments in cancer

“…Indeed, several membrane proteins required for endocytosis become dysfunctional during cancer development, as is the case for CAV1. For instance, CAV1 and dynamin-2, which are both important for caveolamediated endocytosis and caveola assembly, are highly expressed in bladder cancer and possibly contribute to the progression of this type of cancer [134].…”