Contextual cues from cancer cells govern cancer-associated fibroblast heterogeneity
- 주제(키워드) cancer-associated fibroblast , EMT , invasion , lung cancer , metastasis , microRNA , secretion , single-cell RNA sequencing , tumor microenvironment
- 등재 SCIE, SCOPUS
- 발행기관 Elsevier B.V.
- 발행년도 2021
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000181809
- 본문언어 영어
- Published As http://dx.doi.org/10.1016/j.celrep.2021.109009
초록/요약
Cancer cells function as primary architects of the tumor microenvironment. However, the molecular features of cancer cells that govern stromal cell phenotypes remain unclear. Here, we show that cancer-associated fibroblast (CAF) heterogeneity is driven by lung adenocarcinoma (LUAD) cells at either end of the epithelial-to-mesenchymal transition (EMT) spectrum. LUAD cells that have high expression of the EMT-activating transcription factor ZEB1 reprogram CAFs through a ZEB1-dependent secretory program and direct CAFs to the tips of invasive projections through a ZEB1-driven CAF repulsion process. The EMT, in turn, sensitizes LUAD cells to pro-metastatic signals from CAFs. Thus, CAFs respond to contextual cues from LUAD cells to promote metastasis. © 2021 The Author(s)
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