Inactivation of p38 MAPK contributes to stem cell-like properties of non-small cell lung cancer

Autor: Peiqing Sun, Weijun Su, Chen Zhou, Guanwen Wang, Juan Wang, Shaorong Zhao, Shuangtao Zhao, Shan Huang, Rong Xiang, Yan Fang, Pengling Jiang, Peng Wang, Antao Chang
Rok vydání: 2017
Předmět:
Male
0301 basic medicine
Homeobox protein NANOG
Proteasome Endopeptidase Complex
Lung Neoplasms
stemness markers
p38
p38 Mitogen-Activated Protein Kinases
MK2
Kruppel-Like Factor 4
Mice
03 medical and health sciences
0302 clinical medicine
SOX2
Cancer stem cell
Carcinoma
Non-Small-Cell Lung
Cell Line
Tumor
medicine
Animals
Humans
Phosphorylation
Hsp27
Lung cancer
Protein Stability
business.industry
SOXB1 Transcription Factors
Cancer
medicine.disease
3. Good health
Enzyme Activation
Gene Expression Regulation
Neoplastic
Disease Models
Animal
Cell Transformation
Neoplastic
030104 developmental biology
Oncology
KLF4
030220 oncology & carcinogenesis
Proteolysis
Immunology
Cancer cell
Neoplastic Stem Cells
Cancer research
Heterografts
lung cancer stem cells
Stem cell
business
Biomarkers
Research Paper
Zdroj: Oncotarget
ISSN: 1949-2553
Popis: // Yan Fang 1 , Juan Wang 1 , Guanwen Wang 1 , Chen Zhou 1 , Peng Wang 1 , Shuangtao Zhao 1 , Shaorong Zhao 1 , Shan Huang 2 , Weijun Su 1, 2 , Pengling Jiang 3 , Antao Chang 1, 2 , Rong Xiang 1 , Peiqing Sun 1, 2 1 Department of Immunology, School of Medicine, Nankai University, Tianjin, China 2 Department of Cancer Biology and Comprehensive Cancer Center, Wake Forest University Medical Center, Winston-Salem, North Carolina, USA 3 Key Laboratory of Cancer and Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, China Correspondence to: Peiqing Sun, email: psun@wakehealth.edu Rong Xiang, email: rxiang@nankai.edu.cn Keywords: p38, Hsp27, MK2, stemness markers, lung cancer stem cells Received: November 15, 2016 Accepted: February 15, 2017 Published: March 01, 2017 ABSTRACT Cancer stem cells (CSCs) are recognized as the major source for cancer initiation and recurrence. Yet, the mechanism by which the cancer stem cell properties are acquired and maintained in a cancer cell population is not well understood. In the current study, we observed that the level of active p38 MAPK is downregulated, while the level of the stemness marker SOX2 is upregulated in lung cancer tissues as compared to normal tissues. We further demonstrated that inactivation of p38 is a potential mechanism contributing to acquisition and maintenance of cancer stem cell properties in non-small cell lung cancer (NSCLC) cells. p38, in particular the p38γ and p38δ isoforms, suppresses the cancer stem cell properties and tumor initiating ability of NSCLC cells by promoting the ubiquitylation and degradation of stemness proteins such as SOX2, Oct4, Nanog, Klf4 and c-Myc, through MK2-mediated phosphorylation of Hsp27 that is an essential component of the proteasomal degradation machinery. In contrast, inactivation of p38 in lung cancer cells leads to upregulation of the stemness proteins, thus promoting the cancer stem cell properties of these cells. These findings have demonstrated a novel mechanism by which cancer stem cell properties are acquired and maintained in a cancer cell population, and have revealed a new function of the p38 pathway in suppressing cancer development. These studies have also identified a new pathway that can potentially serve as a target for cancer therapies aimed at eliminating CSCs.
Databáze: OpenAIRE
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