Overexpression of flotillin-1 is involved in proliferation and recurrence of bladder transitional cell carcinoma

Abstract

Flotillin-1 (FLOT1) is known to have a role in tumorigenesis; however, the effect of FLOT1 on proliferation and recurrence of human transitional cell carcinoma (TCC) is unclear. Samples from 156 TCC patients and 142 patients undergoing open bladder surgery for indications other than TCC were used in the present study. FLOT1 protein expression was determined by immunohistochemistry and western blot analysis, and mRNA expression was detected by RT-PCR and real-time PCR. A FLOT1-expressing pcDEF3 vector was stably transfected into 4 TCC cell lines and FLOT1 expression was decreased by RNAi. Proliferative analysis of TCC cells was detected by the WST-1 assay and a xenograft model using BALB/C nude mice. The association between FLOT1 expression and TCC recurrence was also analyzed by adhesion, migration and invasion assays. FLOT1 expression in TCC was significantly overexpressed compared to normal urothelial tissue, and the level of FLOT1 expression was significantly correlated with tumor size, pathologic grade, clinical stage and recurrence. In addition, FLOT1 significantly increased the proliferative ability of TCC cells in vitro and in vivo. TCC cells with a high level of FLOT1 expression exhibited a higher level of adhesion, migration and invasion. FLOT1 expression was shown to be upregulated in human TCC. These findings suggest that FLOT1 plays an important role in the proliferation and recurrence of TCC and that silencing FLOT1 expression might be a novel therapeutic strategy.

MicroRNA-608 inhibits proliferation of bladder cancer via AKT/FOXO3a signaling pathway

“…There were two high scoring binding sites of miR-608 on the 3′-UTR of FLOT1 mRNA. It has been reported that FLOT1 was the upstream regulator of AKT/FOXO3a pathway in renal cell cancer and the proliferation regulator in BCa and breast cancer [31, 38, 39]. In our study, we discovered that FLOT1 was widely over-expressed in bladder cancer TMAs (Fig.…”

“…In addtion, FLOT1 was primarily known as a cell signaling mediator by anchoring various receptors of signaling pathways onto cell membrane [48, 49]. Previous studies showed that FLOT1 was constantly overexpressed in various cancers such as colorectal tumor, esophageal squamous carcinoma, tongue squamous carcinoma, prostate cancer, bladder transitional cell carcinoma, renal cell carcinoma and breast cancer [31, 38–40, 50–52]. Moreover, the overexpression of FLOT1 could dramatically promote the proliferation of prostate and bladder cancer cells, and also accelerate the invasion, migration of bladder cancer cells [38, 52].…”

“…Previous studies showed that FLOT1 was constantly overexpressed in various cancers such as colorectal tumor, esophageal squamous carcinoma, tongue squamous carcinoma, prostate cancer, bladder transitional cell carcinoma, renal cell carcinoma and breast cancer [31, 38–40, 50–52]. Moreover, the overexpression of FLOT1 could dramatically promote the proliferation of prostate and bladder cancer cells, and also accelerate the invasion, migration of bladder cancer cells [38, 52]. The expression levels of FLOT1 in bladder and breast cancers were negatively correlated with the prognosis of patients [38, 39].…”

“…Moreover, the overexpression of FLOT1 could dramatically promote the proliferation of prostate and bladder cancer cells, and also accelerate the invasion, migration of bladder cancer cells [38, 52]. The expression levels of FLOT1 in bladder and breast cancers were negatively correlated with the prognosis of patients [38, 39]. Further in vitro experiments proved that the down-regulation of FLOT1 in renal and breast cancers could inhibit the proliferation of cancer cells via activating AKT/FOXO3a signaling pathway [31, 39], which is consistent with the results of our study in bladder cancer cells.…”

Flotilin-1 promotes the tumorigenicity and progression of malignant phenotype in human lung adenocarcinoma

“…14,15,21 Recent studies have revealed that flotillin-1 has important roles in the progression of several tumor types, including hepatocellular carcinoma, 22 neuroblastoma, 23 breast cancer, [24][25][26] tongue squamous cell cancer, 27 esophageal squamous cell carcinoma, [28][29][30] prostate cancer, 19 NSCLC, 5,31,32,33 renal cell carcinoma 34 and bladder transitional cell carcinoma. 35 Zhang SH et al have reported that a high level of flotillin-1 expression is associated with disease progression and poor prognosis in patients with hepatocellular carcinoma. 22 Consistently, our previous study revealed that upregulation of flotillin-1 expression in human LUAD tissues is significantly correlated with advanced clinical stage, lymph node metastasis, increased postoperative relapse and decreased overall survival.…”