Abstract
The tetraspanin protein superfamily participate in the dynamic regulation of cellular membrane compartments expressed in a variety of tumor types, which may alter the biological properties of cancer cells such as cell development, activation, growth and motility. The role of tetraspanin 7 (TSPAN7) has never been investigated in bladder cancer (BCa). In this study, we aimed to investigate the biological function of TSPAN7 and its therapeutic potential in human BCa. First, via reverse transcription and quantitative real-time PCR (qRT-PCR), we observed downregulation of TSPAN7 in BCa tissues samples and cell lines and found that this downregulation was associated with a relatively high tumor stage and tumor grade. Low expression of TSPAN7 was significantly correlated with a much poorer prognosis for BCa patients than was high expression. Immunohistochemistry (IHC) showed that low TSPAN7 expression was a high-risk predictor of BCa patient overall survival. Furthermore, the inhibitory effects of TSPAN7 on the proliferation and migration of BCa cell lines were detected by CCK-8, wound-healing, colony formation and transwell assays in vitro. Flow cytometry analysis revealed that TSPAN7 induced BCa cell lines apoptosis and cell cycle arrest. In vivo, tumor growth in nude mice bearing tumor xenografts could be obviously affected by overexpression of TSPAN7. Western blotting showed that overexpression of TSPAN7 activated Bax, cleaved caspase-3 and PTEN but inactivated Bcl-2, p-PI3K, and p-AKT to inhibit BCa cell growth via the PTEN/PI3K/AKT pathway. Taken together, our study will help identify a potential marker for BCa diagnosis and supply a target molecule for BCa treatment.
Highlights
Bladder cancer (BCa) is the most common malignancy of the urinary system, with more than 80,000 newly diagnosed cases and almost 18,000 deaths in the USA in 2019 [1]
Previous studies have found that in cerebellar granule cells, tetraspanin 7 (TSPAN7) promotes axonal branching, and the size of TSPAN7 clusters is increased by downregulation of IGSF3 expression, which might be at the center of a new signaling pathway controlling brain development [21]
There is research suggesting that TSPAN7 plays an important role in the cytoskeletal organization required for the bone-resorbing function of osteoclasts by regulating signaling to Src, Pyk2, and microtubules [23]
Summary
Bladder cancer (BCa) is the most common malignancy of the urinary system, with more than 80,000 newly diagnosed cases and almost 18,000 deaths in the USA in 2019 [1]. 70% of all diagnosed cases are non–muscle invasive bladder cancer (NMIBC), whereas the remaining cases are classified as muscle-invasive bladder cancer (MIBC). Despite advancements in the development of novel drugs and surgical treatments, approximately 50% of patients with BCa develop metastatic or TSPAN7 Inhibits Bladder Cancer Progression recurrent disease within 2 years of diagnosis [2]. Patients always require long-term follow-up with cystoscopy and computed tomography (CT) scans in case of relapse. The overall survival of BCa patients remains very poor, a better understanding of the molecular mechanisms of bladder carcinogenesis and elucidation of effective methods for predicting the prognosis of BCa are imperative
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