title: Wnt5a and CCL25 promote adult T-cell acute lymphoblastic leukemia cell migration, invasion and metastasis.
abstract: Adult T-cell acute lymphoblastic leukemia (T-ALL) is a refractory leukemia. We previously showed that CCL25/CCR9 promotes T-ALL metastasis. In the present study, we assessed the effects of CCL25 on Wnt expression and the effects of Wnt5a and CCL25 on PI3K/Akt and RhoA activation. Transwell assays and mouse xenograft experiments were utilized to assess the effects of Wnt5a and CCL25 on MOLT4 cell invasion, migration and metastasis. The effects of Wnt5a on MOLT4 cell actin polarization and pseudopodium formation were examined using laser scanning confocal microscopy and scanning electron microscopy. CCL25 induced Wnt5a expression in MOLT4 cells by promoting protein kinase C (PKC) expression and activation. Wnt5a promoted MOLT4 cell migration, invasion, actin polarization, and lamellipodium and filopodia formation via PI3K/Akt-RhoA pathway activation. These effects were rescued by PI3K/Akt or RhoA knockdown or inhibition. Additionally, Wnt5a in cooperation with CCL25 promoted MOLT4 cell mouse liver metastasis and stimulated RhoA activation. These results show that CCL25/CCR9 upregulates Wnt5a by promoting PKC expression and activation in MOLT4 cells. This in turn promotes cell migration and invasion via PI3K/Akt-RhoA signaling, enhancing cell polarization and pseudopodium formation. These findings indicate that the PI3K/Akt-RhoA pathway is likely responsible for Wnt5a-induced adult T-ALL cell migration and invasion.
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei, China.|Department of Clinical Oncology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China.
authors.forename: Xinzhou
authors.initials: X
authors.lastname: Deng
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei, China.
authors.forename: Zhenbo
authors.initials: Z
authors.lastname: Tu
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Xiong
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei, China.
authors.forename: Kingsley
authors.initials: K
authors.lastname: Tembo
authors.affiliation: Department of Hematology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei, China.
authors.forename: Pan
authors.initials: P
authors.lastname: Liu
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Pan
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Xiong
authors.affiliation: Department of Biochemical Engineering, Hubei University of Technology Engineering and Technology College, Wuhan, Hubei, China.
authors.forename: Xiangyong
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Leng
authors.affiliation: Department of Hematology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei, China.
authors.forename: Ruijing
authors.initials: R
authors.lastname: Xiao
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei, China.|Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, Hubei, China.
authors.forename: Qiuping
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D019742:Chemokines, CC / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D064593:Heterografts; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D009361:Neoplasm Invasiveness / Q000473:pathology; D009362:Neoplasm Metastasis; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000473:pathology*; D015398:Signal Transduction / Q000502:physiology*; D000071818:Wnt-5a Protein / Q000378:metabolism*
chemical_list: C108074:CCL25 protein, human; D019742:Chemokines, CC; C085389:WNT5A protein, human; D000071818:Wnt-5a Protein
keywords: CCL25/CCR9; PI3K; RhoA; T-cell acute lymphoblastic leukemia; Wnt5a