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The Interplay between Slow-Cycling, Chemoresistant Cancer Cells and Fibroblasts Creates a Proinflammatory Niche for Tumor Progression

Authors
 Jaebeom Cho  ;  Hyo-Jong Lee  ;  Su Jung Hwang  ;  Hye-Young Min  ;  Han Na Kang  ;  A-Young Park  ;  Seung Yeob Hyun  ;  Jeong Yeon Sim  ;  Ho Jin Lee  ;  Hyun-Ji Jang  ;  Young-Ah Suh  ;  Sungyoul Hong  ;  Young Kee Shin  ;  Hye Ryun Kim  ;  Ho-Young Lee 
Citation
 CANCER RESEARCH, Vol.80(11) : 2257-2272, 2020-06 
Journal Title
 CANCER RESEARCH 
ISSN
 0008-5472 
Issue Date
2020-06
Abstract
Quiescent cancer cells are believed to cause cancer progression after chemotherapy through unknown mechanisms. We show here that human non-small cell lung cancer (NSCLC) cell line-derived, quiescent-like, slow-cycling cancer cells (SCC) and residual patient-derived xenograft (PDX) tumors after chemotherapy experience activating transcription factor 6 (ATF6)-mediated upregulation of various cytokines, which acts in a paracrine manner to recruit fibroblasts. Cancer-associated fibroblasts (CAF) underwent transcriptional upregulation of COX2 and type I collagen (Col-I), which subsequently triggered a slow-to-active cycling switch in SCC through prostaglandin E2 (PGE2)- and integrin/Src-mediated signaling pathways, leading to cancer progression. Both antagonism of ATF6 and cotargeting of Src/COX2 effectively suppressed cytokine production and slow-to-active cell cycling transition in SCC, withholding cancer progression. Expression of COX2 and Col-I and activation of Src were observed in patients with NSCLC who progressed while receiving chemotherapy. Public data analysis revealed significant association between COL1A1 and SRC expression and NSCLC relapse. Overall, these findings indicate that a proinflammatory niche created by the interplay between SCC and CAF triggers tumor progression. SIGNIFICANCE: Cotargeting COX2 and Src may be an effective strategy to prevent cancer progression after chemotherapy.
Full Text
https://cancerres.aacrjournals.org/content/80/11/2257.long
DOI
10.1158/0008-5472.CAN-19-0631
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Hye Ryun(김혜련) ORCID logo https://orcid.org/0000-0002-1842-9070
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/179451
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