Alkaline phosphatase downregulation promotes lung adenocarcinoma metastasis via the c-Myc/RhoA axis

Cancer Cell International

Yu Liu¹  Qipeng Xie²  Zhefeng Lou²  Weiwei Lin²  Lingling Zhao²  He Zhao²  Cong Wang²  Xueli Jiao²  Huirong Zhao²  Haishan Huang²  Lu Liu²  Xing Huang³ 

[1] The First Affiliated Hospital of Wenzhou Medical University, 325035, Wenzhou, Zhejiang, China;Zhejiang Provincial Key Laboratory of Medical Genetics, Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, 325035, Wenzhou, Zhejiang, China;Zhejiang Provincial Key Laboratory of Pancreatic Disease, School of Medicine, the First Affiliated Hospital, Zhejiang University, 310003, Hangzhou, Zhejiang, China;

关键词: ALPL;    Lung adenocarcinoma (LUAD);    C-Myc degradation;    RhoA;    Metastasis;   

DOI  :  10.1186/s12935-021-01919-7

来源: Springer

【 摘 要 】

BackgroundLung adenocarcinoma (LUAD) metastasis significantly reduces patient survival; hence inhibiting the metastatic ability of lung cancer cells will greatly prolong patient survival. Alkaline phosphatase (ALPL), a homodimeric cell surface phosphohydrolase, is reported to play a controversial role in prostate cancer and ovarian cancer cell migration; however, the function of ALPL in LUAD and the related mechanisms remain unclear.MethodsTCGA database was used to analysis the expression of ALPL, and further verification was performed in a cohort of 36 LUAD samples by qPCR and western blot. Soft-agar assay, transwell assay and lung metastasis assay were employed to detect the function of ALPL in LUAD progression. The qPCR, luciferase promoter reporter assay and western blot were used to clarify the molecular mechanisms of ALPL in promoting metastasis in LUAD.ResultsALPL was downregulated in LUAD, and the disease-free survival rate of patients with low ALPL was significantly reduced. Further studies showed that overexpression of ALPL in LUAD cell lines did not significantly affect cell proliferation, but it did significantly attenuate lung metastasis in a mouse model. ALPL downregulation in LUAD led to a decrease in the amount of phosphorylated (p)-ERK. Because p-ERK promotes the classical c-Myc degradation pathway, the decrease in p-ERK led to the accumulation of c-Myc and therefore to an increase in RhoA transcription, which enhanced LUAD cell metastasis.ConclusionALPL specially inhibits the metastasis of LUAD cells by affecting the p-ERK/c-Myc/RhoA axis, providing a theoretical basis for the targeted therapy of clinical LUAD.

【 授权许可】

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