title: LASS2 inhibits growth and invasion of bladder cancer by regulating ATPase activity.
abstract: Homo sapienslongevity assurance homolog 2 of yeast LAG1 (LASS2) is a novel suppressor of human cancer metastasis, and downregulation of LASS2 has been associated with a poor prognosis in patients with bladder cancer (BC). However, the molecular mechanism underlying LASS2-mediated inhibition of tumor invasion and metastasis in BC remains unclear. LASS2 has been reported to directly bind to subunit C of vacuolar H+-ATPase (V-ATPase) in various types of cancer, suggesting that LASS2 may inhibit cancer invasion and metastasis by regulating the function of V-ATPase. The present study investigated the effect of LASS2-specific small interfering (si)RNA on the invasion and metastasis of the RT4 human BC cell line, which has a low metastatic potential, and its functional interaction with V-ATPase. Silencing of LASS2 in RT4 cells was able to increase V-ATPase activity, the extracellular hydrogen ion concentration and, in turn, the activation of secreted matrix metalloproteinase (MMP)-2 and MMP-9, which occurred simultaneously with enhanced cell proliferation, cell survival and cell invasionin vitro, as well as acceleration of BC growthin vivo. In this process, it was found that siRNA-LASS2 treatment was able to suppress cell apoptosis induced by doxorubicin. These findings suggest that silencing of LASS2 may enhance the growth, invasion and metastasis of BC by regulating ATPase activity.
authors.affiliation: Department of Urology, The Second Affiliated Hospital of Kunming Medical University, Yunnan Institute of Urology, Kunming, Yunnan 650101, P.R. China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Urology, The Second Affiliated Hospital of Kunming Medical University, Yunnan Institute of Urology, Kunming, Yunnan 650101, P.R. China.
authors.forename: Yigang
authors.initials: Y
authors.lastname: Zuo
authors.affiliation: Department of Urology, The Second Affiliated Hospital of Kunming Medical University, Yunnan Institute of Urology, Kunming, Yunnan 650101, P.R. China.
authors.forename: Mingxia
authors.initials: M
authors.lastname: Ding
authors.affiliation: Department of Urology, The Second Affiliated Hospital of Kunming Medical University, Yunnan Institute of Urology, Kunming, Yunnan 650101, P.R. China.
authors.forename: Changxing
authors.initials: C
authors.lastname: Ke
authors.affiliation: Department of Urology, The Second Affiliated Hospital of Kunming Medical University, Yunnan Institute of Urology, Kunming, Yunnan 650101, P.R. China.
authors.forename: Ruping
authors.initials: R
authors.lastname: Yan
authors.affiliation: Department of Urology, The Second Affiliated Hospital of Kunming Medical University, Yunnan Institute of Urology, Kunming, Yunnan 650101, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhan
authors.affiliation: Department of Urology, The Second Affiliated Hospital of Kunming Medical University, Yunnan Institute of Urology, Kunming, Yunnan 650101, P.R. China.
authors.forename: Jingyu
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Urology, The Second Affiliated Hospital of Kunming Medical University, Yunnan Institute of Urology, Kunming, Yunnan 650101, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Urology, The Second Affiliated Hospital of Kunming Medical University, Yunnan Institute of Urology, Kunming, Yunnan 650101, P.R. China.
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of Urology, The Second Affiliated Hospital of Kunming Medical University, Yunnan Institute of Urology, Kunming, Yunnan 650101, P.R. China.
authors.forename: Jiansong
authors.initials: J
authors.lastname: Wang
keywords: ATPase activity; bladder cancer; invasion and metastasis; longevity assurance homolog 2 of yeast LAG1