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

Autor:	Qipeng Xie, Xing Huang, Xueli Jiao, Yu Liu, Lingling Zhao, Huirong Zhao, Zhefeng Lou, Lu Liu, He Zhao, Haishan Huang, Cong Wang, Weiwei Lin
Jazyk:	angličtina
Rok vydání:	2021
Předmět:	ALPL Cancer Research RHOA C-Myc degradation Cell Lung adenocarcinoma (LUAD) Metastasis 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Genetics medicine Lung cancer RC254-282 030304 developmental biology 0303 health sciences biology QH573-671 Cell growth Chemistry Neoplasms. Tumors. Oncology. Including cancer and carcinogens RhoA medicine.disease medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Cancer research biology.protein Adenocarcinoma Primary Research Cytology
Zdroj:	Cancer Cell International, Vol 21, Iss 1, Pp 1-13 (2021) Cancer Cell International
ISSN:	1475-2867
Popis:	Background Lung 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. Methods TCGA 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. Results ALPL 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. Conclusion ALPL 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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0f765097300e3498517d16b4e6808821 https://doaj.org/article/2f2f23ac71324574953cf65e041c360f Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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