Contextual cues from cancer cells govern cancer-associated fibroblast heterogeneity

Neus Bota-Rabassedas; Priyam Banerjee; Yichi Niu; Wenjian Cao; Jiayi Luo; Yuanxin Xi; Xiaochao Tan; Kuanwei Sheng; Young Ho Ahn; Sieun Lee; Edwin Roger Parra; Jaime Rodriguez-Canales; Jacob Albritton; Michael Weiger; Xin Liu; Hou Fu Guo; Jiang Yu; B. Leticia Rodriguez; Joshua J.A. Firestone; Barbara Mino; Chad J. Creighton; Luisa M. Solis; Pamela Villalobos; Maria Gabriela Raso; Daniel W. Sazer; Don L. Gibbons; William K. Russell; Gregory D. Longmore; Ignacio I. Wistuba; Jing Wang; Harold A. Chapman; Jordan S. Miller; Chenghang Zong; Jonathan M. Kurie

doi:10.1016/j.celrep.2021.109009

Contextual cues from cancer cells govern cancer-associated fibroblast heterogeneity

Neus Bota-Rabassedas, Priyam Banerjee, Yichi Niu, Wenjian Cao, Jiayi Luo, Yuanxin Xi, Xiaochao Tan, Kuanwei Sheng, Young Ho Ahn, Sieun Lee, Edwin Roger Parra, Jaime Rodriguez-Canales, Jacob Albritton, Michael Weiger, Xin Liu, Hou Fu Guo, Jiang Yu, B. Leticia Rodriguez, Joshua J.A. Firestone, Barbara MinoChad J. Creighton, Luisa M. Solis, Pamela Villalobos, Maria Gabriela Raso, Daniel W. Sazer, Don L. Gibbons, William K. Russell, Gregory D. Longmore, Ignacio I. Wistuba, Jing Wang, Harold A. Chapman, Jordan S. Miller, Chenghang Zong, Jonathan M. Kurie

Department of Molecular Medicine

Research output: Contribution to journal › Article › peer-review

19 Scopus citations

Abstract

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.

Original language	English
Article number	109009
Journal	Cell Reports
Volume	35
Issue number	3
DOIs	https://doi.org/10.1016/j.celrep.2021.109009
State	Published - 20 Apr 2021

Bibliographical note

Publisher Copyright:
© 2021 The Author(s)

Keywords

EMT
cancer-associated fibroblast
invasion
lung cancer
metastasis
microRNA
secretion
single-cell RNA sequencing
tumor microenvironment

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10.1016/j.celrep.2021.109009

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Bota-Rabassedas, N., Banerjee, P., Niu, Y., Cao, W., Luo, J., Xi, Y., Tan, X., Sheng, K., Ahn, Y. H., Lee, S., Parra, E. R., Rodriguez-Canales, J., Albritton, J., Weiger, M., Liu, X., Guo, H. F., Yu, J., Rodriguez, B. L., Firestone, J. J. A., ... Kurie, J. M. (2021). Contextual cues from cancer cells govern cancer-associated fibroblast heterogeneity. Cell Reports, 35(3), Article 109009. https://doi.org/10.1016/j.celrep.2021.109009

@article{c9b61bb990d948fdbc5d863701d1c149,

title = "Contextual cues from cancer cells govern cancer-associated fibroblast heterogeneity",

abstract = "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.",

keywords = "EMT, cancer-associated fibroblast, invasion, lung cancer, metastasis, microRNA, secretion, single-cell RNA sequencing, tumor microenvironment",

author = "Neus Bota-Rabassedas and Priyam Banerjee and Yichi Niu and Wenjian Cao and Jiayi Luo and Yuanxin Xi and Xiaochao Tan and Kuanwei Sheng and Ahn, {Young Ho} and Sieun Lee and Parra, {Edwin Roger} and Jaime Rodriguez-Canales and Jacob Albritton and Michael Weiger and Xin Liu and Guo, {Hou Fu} and Jiang Yu and Rodriguez, {B. Leticia} and Firestone, {Joshua J.A.} and Barbara Mino and Creighton, {Chad J.} and Solis, {Luisa M.} and Pamela Villalobos and Raso, {Maria Gabriela} and Sazer, {Daniel W.} and Gibbons, {Don L.} and Russell, {William K.} and Longmore, {Gregory D.} and Wistuba, {Ignacio I.} and Jing Wang and Chapman, {Harold A.} and Miller, {Jordan S.} and Chenghang Zong and Kurie, {Jonathan M.}",

note = "Publisher Copyright: {\textcopyright} 2021 The Author(s)",

year = "2021",

month = apr,

day = "20",

doi = "10.1016/j.celrep.2021.109009",

language = "English",

volume = "35",

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Bota-Rabassedas, N, Banerjee, P, Niu, Y, Cao, W, Luo, J, Xi, Y, Tan, X, Sheng, K, Ahn, YH, Lee, S, Parra, ER, Rodriguez-Canales, J, Albritton, J, Weiger, M, Liu, X, Guo, HF, Yu, J, Rodriguez, BL, Firestone, JJA, Mino, B, Creighton, CJ, Solis, LM, Villalobos, P, Raso, MG, Sazer, DW, Gibbons, DL, Russell, WK, Longmore, GD, Wistuba, II, Wang, J, Chapman, HA, Miller, JS, Zong, C & Kurie, JM 2021, 'Contextual cues from cancer cells govern cancer-associated fibroblast heterogeneity', Cell Reports, vol. 35, no. 3, 109009. https://doi.org/10.1016/j.celrep.2021.109009

TY - JOUR

T1 - Contextual cues from cancer cells govern cancer-associated fibroblast heterogeneity

AU - Bota-Rabassedas, Neus

AU - Banerjee, Priyam

AU - Niu, Yichi

AU - Cao, Wenjian

AU - Luo, Jiayi

AU - Xi, Yuanxin

AU - Tan, Xiaochao

AU - Sheng, Kuanwei

AU - Ahn, Young Ho

AU - Lee, Sieun

AU - Parra, Edwin Roger

AU - Rodriguez-Canales, Jaime

AU - Albritton, Jacob

AU - Weiger, Michael

AU - Liu, Xin

AU - Guo, Hou Fu

AU - Yu, Jiang

AU - Rodriguez, B. Leticia

AU - Firestone, Joshua J.A.

AU - Mino, Barbara

AU - Creighton, Chad J.

AU - Solis, Luisa M.

AU - Villalobos, Pamela

AU - Raso, Maria Gabriela

AU - Sazer, Daniel W.

AU - Gibbons, Don L.

AU - Russell, William K.

AU - Longmore, Gregory D.

AU - Wistuba, Ignacio I.

AU - Wang, Jing

AU - Chapman, Harold A.

AU - Miller, Jordan S.

AU - Zong, Chenghang

AU - Kurie, Jonathan M.

PY - 2021/4/20

Y1 - 2021/4/20

N2 - 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.

AB - 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.

KW - EMT

KW - cancer-associated fibroblast

KW - invasion

KW - lung cancer

KW - metastasis

KW - microRNA

KW - secretion

KW - single-cell RNA sequencing

KW - tumor microenvironment

UR - http://www.scopus.com/inward/record.url?scp=85104303878&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2021.109009

DO - 10.1016/j.celrep.2021.109009

M3 - Article

C2 - 33882319

AN - SCOPUS:85104303878

SN - 2211-1247

VL - 35

JO - Cell Reports

JF - Cell Reports

IS - 3

M1 - 109009

ER -

Contextual cues from cancer cells govern cancer-associated fibroblast heterogeneity

Abstract

Bibliographical note

Keywords

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