Journal article
Wnt5a Increases Properties of Lung Cancer Stem Cells and Resistance to Cisplatin through Activation of Wnt5a/PKC Signaling Pathway
Stem cells international, Vol.2016, pp.1-16
2016
DOI: 10.1155/2016/1690896
PMCID: PMC5118537
PMID: 27895670
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 chemoresistance was 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 cisplatin via a 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.
Details
- Title: Subtitle
- Wnt5a Increases Properties of Lung Cancer Stem Cells and Resistance to Cisplatin through Activation of Wnt5a/PKC Signaling Pathway
- Creators
- Jiali Yang - The Center of Laboratory Medicine, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, ChinaKangjian Zhang - Department of Laboratory Medicine, College of Clinical Medicine, Ningxia Medical University, Yinchuan, Ningxia 750004, ChinaJing Wu - Department of Laboratory Medicine, College of Clinical Medicine, Ningxia Medical University, Yinchuan, Ningxia 750004, ChinaJuan Shi - The Center of Laboratory Medicine, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, ChinaJing Xue - College of Life Science, Ningxia University, Yinchuan, Ningxia 750021, ChinaJing Li - Department of Thoracic Surgery of General Hospital, Ningxia Medical University, Yinchuan, Ningxia 750004, ChinaJuan Chen - Department of Pulmonary and Critical Care Medicine of General Hospital, Ningxia Medical University, Yinchuan 750004, ChinaYongzhao Zhu - Human Stem Cell Institute of General Hospital, Ningxia Medical University, Yinchuan, Ningxia 750004, ChinaJun Wei - 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, ChinaJinxi He - Department of Laboratory Medicine, College of Clinical Medicine, Ningxia Medical University, Yinchuan, Ningxia 750004, ChinaXiaoming Liu - College of Life Science, Ningxia University, Yinchuan, Ningxia 750021, China, Human Stem Cell Institute of General Hospital, Ningxia Medical University, Yinchuan, Ningxia 750004, China
- Resource Type
- Journal article
- Publication Details
- Stem cells international, Vol.2016, pp.1-16
- DOI
- 10.1155/2016/1690896
- PMID
- 27895670
- PMCID
- PMC5118537
- NLM abbreviation
- Stem Cells Int
- ISSN
- 1687-966X
- eISSN
- 1687-9678
- Grant note
- DOI: 10.13039/501100004772, name: Natural Science Foundation of Ningxia Province, award: NZ15277, NZ16155, XM2015090, 31472191
- Language
- English
- Date published
- 2016
- Academic Unit
- Anatomy and Cell Biology
- Record Identifier
- 9984025453402771
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