Serglycin in tumor microenvironment promotes non-small cell lung cancer aggressiveness in a CD44-dependent manner

doi:10.1038/onc.2016.404

CNU IR > Pharmacy and Science > Dept. of Biotechnology (including master's program) > Periodical Articles > Item 310902800/31739

Please use this identifier to cite or link to this item: https://ir.cnu.edu.tw/handle/310902800/31739

Title:	Serglycin in tumor microenvironment promotes non-small cell lung cancer aggressiveness in a CD44-dependent manner
Authors:	Guo, J-Y Hsu, H-S Tyan, S-W Li, F-Y Shew, J-Y Lee, W-H Chen, J-Y
Contributors:	Acad Sinica, Inst Biomed Sci Taipei Vet Gen Hosp, Dept Thorac Surg Chia Nan Univ Pharm & Sci, Dept Biotechnol Taipei Vet Gen Hosp, Dept Pathol Acad Sinica, Genom Res Ctr China Med Univ, Inst Clin Med Natl Yang Ming Univ, Dept Life Sci Natl Yang Ming Univ, Inst Genome Sci
Keywords:	Epithelial-Mesenchymal Transition Nf-Kappa-B Hepatocellular-Carcinoma Colon-Cancer Cd44 Fibroblasts Expression Overexpression Activation Adhesion
Date:	201-04-277
Issue Date:	2018-11-30 15:54:53 (UTC+8)
Publisher:	Nature Publishing Group
Abstract:	Tumor microenvironment (TME) plays an active role in promoting tumor progression. To further understand the communication between TME and tumor cells, this study aimed at investigating the involvement of CD44, a type I cell surface receptor, in the crosstalk between tumor cells and TME. We have previously shown that chondroitin sulfate proteoglycan serglycin (SRGN), a CD44-interacting factor, was preferentially secreted by cancer-associated fibroblasts (CAFs) for promoting tumor growth in breast cancer patients. In this study, we show that SRGN is overexpressed in primary non-small cell lung cancers (NSCLCs), by both carcinoma and stromal cells. Using gain-of-function and loss-of-function approaches, we show that SRGN promotes NSCLC cell migration and invasion as well as colonization in the lung and liver in a CD44-dependent manner. SRGN induces lung cancer cell stemness, as demonstrated by its ability to enhance NSCLC cell sphere formation via Nanog induction, accompanied with increased chemoresistance and anoikis-resistance. SRGN promotes epithelial-mesenchymal transition by enhancing vimentin expression via CD44/NF-kappa B/claudin-1(CLDN1) axis. In support, CLDN1 and SRGN expression are tightly linked together in primary NSCLC. Most importantly, increased expression of SRGN and/or CLDN1 predicts poor prognosis in primary lung adenocarcinomas. In summary, we demonstrate that SRGN secreted by tumor cells and stromal components in the TME promotes malignant phenotypes through interacting with tumor cell receptor CD44, suggesting that a combined therapy targeting both CD44 and its ligands in the TME may be an attractive approach for cancer therapy.
Relation:	Oncogene, v.36, n.17, pp.2457-2471
Appears in Collections:	[Dept. of Biotechnology (including master's program)] Periodical Articles

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