title: PAK1-cofilin phosphorylation mediates human lung adenocarcinoma cells migration induced by apelin-13.
abstract: Adipocytokines apelin peptide, the ligand of APJ (putative receptor related to the angiotensin receptor AT1), plays key roles in the pathogenesis and deterioration of cancer. In lung cancer, apelin elevating microvessel densities has been reported. Our previous research has characterized that apelin-13 promoted lung adenocarcinoma cell proliferation. However, the effect of apelin on metastasis in lung adenocarcinoma and the underlying mechanisms remain unclear. This study shows that apelin-13 induced human adenocarcinoma cell migration via the APJ receptor. Apelin-13 phosphorylated PAK1 and cofilin increase the migration of lung adenocarcinoma cells. Moreover, the results verify that over-expression of apelin and APJ contributed to reducing the effect of doxorubicin and razoxane on inhibiting lung adenocarcinoma cells metastasis. Hypoxia activated APJ expression and apelin release in lung adenocarcinoma cells. The results demonstrate a PAK1-cofilin phosphorylation mechanism to mediate lung adenocarcinoma cells migration promoted by apelin-13. This discovery further suggests that APJ and its downstream signalling is a potential target for anti-metastatic therapies in lung adenocarcinoma patients.
authors.affiliation: Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmacoproteomics, University of South China, Hengyang, China.
authors.forename: Deguan
authors.initials: D
authors.lastname: Lv
authors.affiliation: Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmacoproteomics, University of South China, Hengyang, China.
authors.forename: Lanfang
authors.initials: L
authors.lastname: Li
authors.affiliation: Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmacoproteomics, University of South China, Hengyang, China.
authors.forename: Qixuan
authors.initials: Q
authors.lastname: Lu
authors.affiliation: Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmacoproteomics, University of South China, Hengyang, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Li
authors.affiliation: Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmacoproteomics, University of South China, Hengyang, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Xie
authors.affiliation: Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmacoproteomics, University of South China, Hengyang, China.
authors.forename: Hening
authors.initials: H
authors.lastname: Li
authors.affiliation: Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmacoproteomics, University of South China, Hengyang, China.
authors.forename: Jiangang
authors.initials: J
authors.lastname: Cao
authors.affiliation: Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmacoproteomics, University of South China, Hengyang, China.
authors.forename: Meiqing
authors.initials: M
authors.lastname: Liu
authors.affiliation: Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmacoproteomics, University of South China, Hengyang, China.
authors.forename: Di
authors.initials: D
authors.lastname: Wu
authors.affiliation: Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmacoproteomics, University of South China, Hengyang, China.
authors.forename: Lu
authors.initials: L
authors.lastname: He
authors.affiliation: Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmacoproteomics, University of South China, Hengyang, China.
authors.forename: Linxi
authors.initials: L
authors.lastname: Chen
mesh_terms: D051339:Actin Depolymerizing Factors / Q000378:metabolism*; D000230:Adenocarcinoma / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D000075244:Apelin Receptors; D015687:Cell Hypoxia / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000473:pathology*; D010766:Phosphorylation / Q000187:drug effects; D011929:Razoxane / Q000494:pharmacology; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D054462:p21-Activated Kinases / Q000378:metabolism*
chemical_list: C104575:APLNR protein, human; D051339:Actin Depolymerizing Factors; D000075244:Apelin Receptors; D036341:Intercellular Signaling Peptides and Proteins; D043562:Receptors, G-Protein-Coupled; C495199:apelin-13 peptide; D011929:Razoxane; D004317:Doxorubicin; C515903:PAK1 protein, human; D054462:p21-Activated Kinases
keywords: APJ; PAK1; apelin; cofilin; drug resistance; hypoxia; lung adenocarcinoma; migration