Knockdown of TRPM7 prevents tumor growth, migration, and invasion through the Src, Akt, and JNK pathway in bladder cance
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RESEARCH ARTICLE
Open Access
Knockdown of TRPM7 prevents tumor growth, migration, and invasion through the Src, Akt, and JNK pathway in bladder cancer Eun Hye Lee1†, So Young Chun2†, Bomi Kim2, Bo Hyun Yoon2, Jun Nyung Lee1,3,4, Bum Soo Kim1,3,5, Eun Sang Yoo3,5, Sangkyu Lee6, Phil Hyun Song7, Tae Gyun Kwon1,3,4* and Yun-Sok Ha1,3,4*
Abstract Background: Bladder cancer (BC) is one of the most common malignancies of the urinary tract. The role of transient receptor potential melastatin 7 (TRPM7) in BC remains unclear. The aim of this study was to investigate the function and signal transduction pathway of TRPM7 in BC. Methods: T24 and UMUC3 cells were used to evaluate the molecular mechanism of TRPM7 by immunoblot analysis. Small interfering RNA was used to knockdown TRPM7, and the effect of silencing TRPM7 was studied by wound healing, migration, and invasion assays in T24 and UMUC3 cells. Xenograft model study was obtained to analyze the effect of TRPM7 inhibition in vivo. Results: Silencing of TRPM7 decreased the migration and invasion ability of T24 and UMUC3 cells. The phosphorylation of Src, Akt, and JNK (c-Jun N-terminal kinase) was also suppressed by TRPM7 silencing. Src, Akt, and JNK inhibitors effectively inhibited the migration and invasion of T24 and UMUC3 cells. In addition, the TRPM7 inhibitor, carvacrol, limited the tumor size in a xenograft model. Conclusion: Our data reveal that TRPM7 regulates the migration and invasion of T24 and UMUC3 cells via the Src, Akt, and JNK signaling pathway. Therefore, TRPM7 suppression could be a potential treatment for BC patients. Keywords: Bladder cancer, TRPM7, Src, Akt, JNK
Background Bladder cancer (BC) is a critical public health issue, and is known as the most common cancer of the urinary tract and the ninth most common cause of cancer related death worldwide [1]. There are approximately 400,000 cases of BC and 150,000 deaths * Correspondence: [email protected]; [email protected] † Eun Hye Lee and So Young Chun contributed equally to this work. 1 Joint Institute for Regenerative Medicine, Kyungpook National University Hospital, Daegu, Republic of Korea Full list of author information is available at the end of the article
per year [2]. The incidence of BC rises with age and the incidence is three times greater in in men than women. The most common symptom of BC is hematuria without pain [3], and BC is commonly diagnosed by cystoscopy and cytology [4]. The pathologic type of BC can be divided into two groups: non-muscle invasive BC (NMIBC) and muscle invasive BC (MIBC) [5]. NMIBC includes Ta and T1 stages, which are a low grade non-invasive papillary tumors that penetrate the basement membrane without invading the muscle layer of the bladder wall.
© The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link
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