Extracellular serglycin upregulates the CD44 receptor in an autocrine manner to maintain self-renewal in nasopharyngeal carcinoma cells by reciprocally activating the MAPK/β-catenin axis

Autor: Simei Shi, Li-Xia Peng, Xinjian Li, Hongbing Huang, Li-Sheng Zheng, C.N. Qian, Tie Jun Huang, Qiaoqiao Chu, Li Cao, Bi-Jun Huang, Liang Xu, Shi-Jun Zhang, Jialing Huang
Rok vydání: 2016
Předmět:
0301 basic medicine
MAPK/ERK pathway
Cancer Research
MAP Kinase Signaling System
Receptor expression
Immunology
Vesicular Transport Proteins
Down-Regulation
Models
Biological
Mice
03 medical and health sciences
Cellular and Molecular Neuroscience
Downregulation and upregulation
Cancer stem cell
Cell Line
Tumor
otorhinolaryngologic diseases
Animals
Humans
Serglycin
Cell Self Renewal
Neoplasm Metastasis
Extracellular Signal-Regulated MAP Kinases
Autocrine signalling
beta Catenin
Feedback
Physiological
Nasopharyngeal Carcinoma
biology
Carcinoma
CD44
Nasopharyngeal Neoplasms
Cell Biology
Up-Regulation
Autocrine Communication
Protein Transport
stomatognathic diseases
Hyaluronan Receptors
030104 developmental biology
Gene Knockdown Techniques
Catenin
Neoplastic Stem Cells
Cancer research
biology.protein
Proteoglycans
Original Article
Extracellular Space
Zdroj: Cell Death & Disease
ISSN: 2041-4889
Popis: Serglycin is a proteoglycan that was first found to be secreted by hematopoietic cells. As an extracellular matrix (ECM) component, serglycin promotes nasopharyngeal carcinoma (NPC) metastasis and serves as an independent, unfavorable NPC prognostic indicator. The detailed mechanism underlying the roles of serglycin in cancer progression remains to be clarified. Here, we report that serglycin knockdown in NPC cells inhibited cell sphere formation and tumor seeding abilities. Serglycin downregulation enhanced high-metastasis NPC cell sensitivity to chemotherapy. It has been reported that serglycin is a novel ligand for the stem cell marker CD44. Interestingly, we found a positive correlation between serglycin expression and CD44 in nasopharyngeal tissues and NPC cell lines. Further study revealed that CD44 was an ERK-dependent downstream effector of serglycin signaling, and serglycin activated the MAPK/β-catenin axis to induce CD44 receptor expression in a positive feedback loop. Taken together, our novel findings suggest that ECM serglycin upregulated CD44 receptor expression to maintain NPC stemness by interacting with CD44 and activating the MAPK/β-catenin pathway, resulting in NPC cell chemoresistance. These findings suggest that the intervention of serglycin/CD44 axis and downstream signaling pathway is a rational strategy for targeting NPC cancer stem cell therapy.
Databáze: OpenAIRE
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