title: Wnt5a Increases Properties of Lung Cancer Stem Cells and Resistance to Cisplatin through Activation of Wnt5a/PKC Signaling Pathway.
abstract: The development of chemoresistance to cisplatin regimens causes a poor prognosis in patients with advanced NSCLC. The role of noncanonical Wnt signaling in the regulation of properties of lung cancer stem cells and chemoresistancewas interrogated, by accessing capacities of cell proliferation, migration, invasion, and clonogenicity as well as the apoptosis in A549 cell lines and cisplatin-resistant A549 cells treated with Wnt5a conditional medium or protein kinase C (PKC) inhibitor GF109203X. Results showed that the noncanonical Wnt signaling ligand, Wnt5a, could promote the proliferation, migration, invasion, and colony formation in A549 lung adenocarcinoma cells and cisplatin-resistant A549/DDP cells and increase the fraction of ALDH-positive cell in A549/DDP cells. An exposure of cells to Wnt5a led to a significant reduction of A549/DDP cell apoptosis but not A549 cells. An addition of GF109203X could both strikingly increase the baseline apoptosis and resensitize the Wnt5a-inhibited cell apoptosis. Interestingly, an inhibition of Wnt/PKC signaling pathway could reduce properties of lung cancer stem cells, promote cell apoptosis, and resensitize cisplatin-resistant cells to cisplatinviaa caspase/AIF-dependent pathway. These data thus suggested that the Wnt5a could promote lung cancer cell mobility and cisplatin-resistance through a Wnt/PKC signaling pathway and a blockage of this signaling may be an alternative therapeutic strategy for NSCLC patients with resistance to chemotherapies.
authors.affiliation: The Center of Laboratory Medicine, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, China.
authors.forename: Jiali
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Laboratory Medicine, College of Clinical Medicine, Ningxia Medical University, Yinchuan, Ningxia 750004, China.
authors.forename: Kangjian
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Laboratory Medicine, College of Clinical Medicine, Ningxia Medical University, Yinchuan, Ningxia 750004, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.affiliation: The Center of Laboratory Medicine, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Shi
authors.affiliation: College of Life Science, Ningxia University, Yinchuan, Ningxia 750021, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xue
authors.affiliation: Department of Thoracic Surgery of General Hospital, Ningxia Medical University, Yinchuan, Ningxia 750004, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Pulmonary and Critical Care Medicine of General Hospital, Ningxia Medical University, Yinchuan 750004, China.
authors.forename: Juan
authors.identifier: 0000-0001-5801-9124
authors.initials: J
authors.lastname: Chen
authors.affiliation: Human Stem Cell Institute of General Hospital, Ningxia Medical University, Yinchuan, Ningxia 750004, China.
authors.forename: Yongzhao
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: The Center of Laboratory Medicine, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, China; Human Stem Cell Institute of General Hospital, Ningxia Medical University, Yinchuan, Ningxia 750004, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wei
authors.affiliation: Department of Laboratory Medicine, College of Clinical Medicine, Ningxia Medical University, Yinchuan, Ningxia 750004, China.
authors.forename: Jinxi
authors.identifier: 0000-0001-8377-5474
authors.initials: J
authors.lastname: He
authors.affiliation: College of Life Science, Ningxia University, Yinchuan, Ningxia 750021, China; Human Stem Cell Institute of General Hospital, Ningxia Medical University, Yinchuan, Ningxia 750004, China.
authors.forename: Xiaoming
authors.identifier: 0000-0002-3902-9105
authors.initials: X
authors.lastname: Liu