LASS2 inhibits growth and invasion of bladder cancer by regulating ATPase activity.
LASS2 inhibits growth and invasion of bladder cancer by regulating ATPase activity.
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LASS2通过调节ATP酶活性抑制膀胱癌的生长和侵袭
DOI：
10.3892/ol.2016.5514
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发表时间：
2017-02
期刊：
影响因子：
2.9
通讯作者：
Wang J
中科院分区：
文献类型：
--
作者：
Wang H;Zuo Y;Ding M;Ke C;Yan R;Zhan H;Liu J;Wang W;Li N;Wang J
酵母LAG 1的人类长寿保证同源物2（LASS 2）是一种新的人类癌症转移抑制剂，并且LASS 2的下调与膀胱癌（BC）患者的不良预后相关。然而，LASS 2介导的抑制BC中肿瘤侵袭和转移的分子机制仍不清楚。在多种肿瘤中，LASS 2可与液泡H+-ATP酶（V-ATP酶）的C亚基结合，提示LASS 2可能通过调节V-ATP酶的功能来抑制肿瘤的侵袭和转移。本研究探讨了LASS 2特异性小干扰（si）RNA对RT 4人BC细胞系的侵袭和转移的影响，该细胞系具有低转移潜力，以及其与V-ATP酶的功能相互作用。RT 4细胞中LASS 2的沉默能够增加V-ATP酶活性，细胞外氢离子浓度，进而激活分泌的基质金属蛋白酶（MMP）-2和MMP-9，这与体外增强的细胞增殖，细胞存活和细胞侵袭同时发生，以及体内BC生长的加速。在此过程中，发现siRNA-LASS 2处理能够抑制阿霉素诱导的细胞凋亡。提示LASS 2基因沉默可能通过调节ATP酶活性促进BC的生长、侵袭和转移。
Homo sapiens longevity 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 invasion in vitro, as well as acceleration of BC growth in 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.