PMID- 27819672
DCOM- 20170901
LR  - 20180511
IS  - 1476-5594 (Electronic)
IS  - 0950-9232 (Linking)
VI  - 36
IP  - 17
DP  - 2017 Apr 27
TI  - Serglycin in tumor microenvironment promotes non-small cell lung cancer
      aggressiveness in a CD44-dependent manner.
PG  - 2457-2471
LID - 10.1038/onc.2016.404 [doi]
AB  - 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-kappaB/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.
FAU - Guo, J-Y
AU  - Guo JY
AD  - Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
FAU - Hsu, H-S
AU  - Hsu HS
AD  - Department of Thoracic Surgery, Taipei Veterans General Hospital, Taipei, Taiwan.
FAU - Tyan, S-W
AU  - Tyan SW
AD  - Department of Biotechnology, Chia Nan University of Pharmacy & Science, Tainan,
FAU - Li, F-Y
AU  - Li FY
AD  - Department of Pathology, Taipei Veterans General Hospital, Taipei, Taiwan.
FAU - Shew, J-Y
AU  - Shew JY
AD  - Genomics Research Center, Academia Sinica, Taipei, Taiwan.
FAU - Lee, W-H
AU  - Lee WH
AD  - Genomics Research Center, Academia Sinica, Taipei, Taiwan.
AD  - Institute of Clinical Medicine, China Medical University, Taichung, Taiwan.
FAU - Chen, J-Y
AU  - Chen JY
AD  - Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
AD  - Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming 
      University, Taipei, Taiwan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20161107
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Claudin-1)
RN  - 0 (Hyaluronan Receptors)
RN  - 0 (NF-kappa B)
RN  - 0 (Proteoglycans)
RN  - 0 (Vesicular Transport Proteins)
RN  - 0 (serglycin)
SB  - IM
MH  - Carcinoma, Non-Small-Cell Lung/*pathology
MH  - Cell Line, Tumor
MH  - Claudin-1/metabolism
MH  - Epithelial-Mesenchymal Transition
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Hyaluronan Receptors/*metabolism
MH  - Lung Neoplasms/*pathology
MH  - NF-kappa B/metabolism
MH  - Phenotype
MH  - Proteoglycans/*metabolism
MH  - Survival Analysis
MH  - *Tumor Microenvironment
MH  - Vesicular Transport Proteins/*metabolism
PMC - PMC5415946
EDAT- 2016/11/08 06:00
MHDA- 2017/09/02 06:00
CRDT- 2016/11/08 06:00
PHST- 2016/04/01 00:00 [received]
PHST- 2016/08/20 00:00 [revised]
PHST- 2016/09/19 00:00 [accepted]
PHST- 2016/11/08 06:00 [pubmed]
PHST- 2017/09/02 06:00 [medline]
PHST- 2016/11/08 06:00 [entrez]
AID - onc2016404 [pii]
AID - 10.1038/onc.2016.404 [doi]
PST - ppublish
SO  - Oncogene. 2017 Apr 27;36(17):2457-2471. doi: 10.1038/onc.2016.404. Epub 2016 Nov