LMTK3 promotes tumorigenesis in bladder cancer via the ERK/MAPK pathway. Issue 10 (16th September 2020)

• Record Type: Journal Article
• Authors: Jiang, Tao; Lu, Xinxing; Yang, Feiya; Wang, Mingshuai; Yang, Hua; Xing, Nianzeng
• Is Part Of: FEBS open bio. Volume 10:Issue 10(2020)
• Page Start: 2107
• Page End: 2121
• Publication Date: 2020-09-16
• Subjects: biomarker -- bladder cancer -- lemur tyrosine kinase‐3 -- weighted gene coexpression network analysis; Molecular biology -- Periodicals; Cytology -- Periodicals; Life sciences -- Periodicals; Biological Science Disciplines -- Periodicals; Molecular Biology -- Periodicals; Cell Biology -- Periodicals; Cytology; Life sciences; Molecular biology; Periodicals; 572.805
• DOI: 10.1002/2211-5463.12964
• Languages: English
• ISSNs: 2211-5463

Abstract

Abstract : Lemur tyrosine kinase 3 (LMTK3) is a key member of the serine–threonine tyrosine kinase family. It plays an important role in breast cancer tumorigenesis and progression. However, its biological role in bladder cancer remains elusive. In this study, we demonstrated that LMTK3 was overexpressed in bladder cancer and was positively correlated with bladder cancer malignancy. High LMTK3 expression predicted poor overall survival. Knockdown of LMTK3 in bladder cancer cells triggered cell‐cycle arrest at G2/M phase, suppressed cell growth, and induced cell apoptosis in bladder cancer cells. Furthermore, Transwell assays revealed that reduction of LMTK3 decreased cell migration by regulating the epithelial‐to‐mesenchymal transition pathway. Conversely, LKTM3 overexpression was shown to promote proliferation and migration of bladder cancer cells. We assessed phosphorylation of MEK and ERK1/2 in bladder cancer cells depleted of LMTK3 and demonstrated a reduced phosphorylation status compared with the control group. Using an MAPK signaling‐specific inhibitor, U0126, we could rescue the promotion of proliferation and viability in LMTK3‐overexpressing cells. In conclusion, we extend the status of LMTK3 as an oncogene in bladder cancer and provide evidence for its function via the activation of the ERK/MAPK pathway. Thus, targeting LMTK3 may hold potential as a diagnostic and prognostic biomarker and as a possible future treatment for bladder cancer. Abstract : Here, we characterise LMTK3 as an oncogene in bladder cancer. LMTK3 was overexpressed in bladder cancer and this increased expression closely correlated with poor survival of bladder cancer patients. LMTK3 overexpression induced cell growth and migration whereas its depletion promoted apoptosis of bladder cancer cells. We found LMTK3 promoted tumorigenesis and progression by activating the ERK/MAPK pathway.