KLHL38 involvement in non-small cell lung cancer progression via activation of the Akt signaling pathway

被引:11
作者
Xu, Yitong [1 ]
Wang, Chenglong [2 ]
Jiang, Xizi [3 ]
Zhang, Yao [3 ]
Su, Hongbo [1 ]
Jiang, Jun [4 ]
Ren, Hongjiu [3 ]
Qiu, Xueshan [1 ,3 ]
机构
[1] China Med Univ, Affiliated Hosp 1, Dept Pathol, Shenyang 110000, Peoples R China
[2] China Med Univ, Affiliated Hosp 1, Dept Pain Med, Shenyang 110000, Peoples R China
[3] China Med Univ, Coll Basic Med Sci, Dept Pathol, Shenyang 110000, Peoples R China
[4] Jilin Univ, Bethune Hosp 1, Dept Pathol, Changchun 130000, Jilin, Peoples R China
基金
中国国家自然科学基金;
关键词
GENETIC ALTERATIONS; MIGRATION; INVASION; PTEN; RESISTANCE; EXPRESSION;
D O I
10.1038/s41419-021-03835-0
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Lung cancer is the leading cause of cancer-related death worldwide. KLHL38 has been reported to be upregulated during diapause but downregulated after androgen treatment during the reversal of androgen-dependent skeletal muscle atrophy. This study aimed to clarify the role of KLHL38 in non-small cell lung cancer (NSCLC). KLHL38 expression was evaluated in tumor and adjacent normal tissues from 241 patients with NSCLC using immunohistochemistry and real-time PCR, and its association with clinicopathological parameters was analyzed. KLHL38 levels positively correlated with tumor size, lymph node metastasis, and pathological tumor-node-metastasis stage (all P < 0.001). In NSCLC cell lines, KLHL38 overexpression promoted PTEN ubiquitination, thereby activating Akt signaling. It also promoted cell proliferation, migration, and invasion by upregulating the expression of genes encoding cyclin D1, cyclin B, c-myc, RhoA, and MMP9, while downregulating the expression of p21 and E-cadherin. In vivo experiments in nude mice further confirmed that KLHL38 promotes NSCLC progression through Akt signaling pathway activation. Together, these results indicate that KLHL38 is a valuable candidate prognostic biomarker and potential therapeutic target for NSCLC.
引用
收藏
页数:14
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