Tumor suppressor LHPP regulates the proliferation of colorectal cancer cells via the PI3K/AKT pathway

被引:50
作者
Hou, Bin [1 ]
Li, Wenhan [2 ,3 ]
Li, Jianhui [2 ,3 ]
Ma, Jia [2 ,3 ]
Xia, Peng [1 ]
Liu, Zhao [1 ]
Zeng, Qingnuo [1 ]
Zhang, Xin [1 ]
Chang, Dongmin [1 ]
机构
[1] Xi An Jiao Tong Univ, Dept Surg Oncol, Affiliated Hosp 1, 277 W Yanta Rd, Xian 710061, Shaanxi, Peoples R China
[2] Shaanxi Prov Peoples Hosp, Dept Surg Oncol, Xian 10068, Shaanxi, Peoples R China
[3] Xi An Jiao Tong Univ, Sch Med, Affiliated Hosp 3, Xian 710061, Shaanxi, Peoples R China
关键词
colorectal cancer; LHPP; PI3K; AKT signaling pathway; proliferation; PROTEIN HISTIDINE PHOSPHATASE; INORGANIC PYROPHOSPHATASE; SIGNALING PATHWAY; PIK3CA GENE; CYCLE; 3-PHOSPHOHISTIDINE; EXPRESSION; MUTATIONS; NM23-H1; GROWTH;
D O I
10.3892/or.2019.7442
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the fourth leading cause of cancer-related mortality worldwide. Thus, identification of the mechanisms involved in the progression of CRC has become a crucial element of facilitating early CRC diagnosis and targeted therapy for patients with advanced CRC. Currently, Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP), a type of histidine phosphatase protein, has been confirmed as a tumor suppressor in hepatocellular carcinoma (HCC) and cervical cancer. However, the functions and molecular mechanisms underlying LHPP in CRC remain undefined. The present study revealed that dysregulation of LHPP was frequently observed in CRC tissues and was positively correlated with tumor severity and poor prognosis. Functional experiments demonstrated that overexpression of LHPP impeded CRC cell growth and proliferation in vitro, and was associated with a change in p53 expression and PI3K/AKT activity. In contrast, silencing of LHPP significantly promoted cell growth and proliferation by modulating the PI3K/AKT signaling pathway. Notably, the anti-CRC effects of LHPP were also observed in nude mouse in vivo experiments. Overall, the data obtained in the present study suggested that LHPP may be exploited as a diagnostic and prognostic candidate for patients with CRC.
引用
收藏
页码:536 / 548
页数:13
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