TY - JOUR
T1 - Tumor-initiating cells establish an IL-33–TGF-b niche signaling loop to promote cancer progression
AU - Taniguchi, Sachiko
AU - Elhance, Ajit
AU - van Duzer, Avery
AU - Kumar, Sushil
AU - Leitenberger, Justin J.
AU - Oshimori, Naoki
N1 - Publisher Copyright:
© 2020 American Association for the Advancement of Science. All rights reserved.
PY - 2020/7/17
Y1 - 2020/7/17
N2 - Targeting the cross-talk between tumor-initiating cells (TICs) and the niche microenvironment is an attractive avenue for cancer therapy. We show here, using a mouse model of squamous cell carcinoma, that TICs play a crucial role in creating a niche microenvironment that is required for tumor progression and drug resistance. Antioxidant activity in TICs, mediated by the transcription factor NRF2, facilitates the release of a nuclear cytokine, interleukin-33 (IL-33). This cytokine promotes differentiation of macrophages that express the high-affinity immunoglobulin E receptor FceRIa and are in close proximity to TICs. In turn, these IL-33–responding FceRIa+ macrophages send paracrine transforming growth factor b (TGF-b) signals to TICs, inducing invasive and drug-resistant properties and further upregulating IL-33 expression. This TIC-driven, IL-33–TGF-b feedforward loop could potentially be exploited for cancer treatment.
AB - Targeting the cross-talk between tumor-initiating cells (TICs) and the niche microenvironment is an attractive avenue for cancer therapy. We show here, using a mouse model of squamous cell carcinoma, that TICs play a crucial role in creating a niche microenvironment that is required for tumor progression and drug resistance. Antioxidant activity in TICs, mediated by the transcription factor NRF2, facilitates the release of a nuclear cytokine, interleukin-33 (IL-33). This cytokine promotes differentiation of macrophages that express the high-affinity immunoglobulin E receptor FceRIa and are in close proximity to TICs. In turn, these IL-33–responding FceRIa+ macrophages send paracrine transforming growth factor b (TGF-b) signals to TICs, inducing invasive and drug-resistant properties and further upregulating IL-33 expression. This TIC-driven, IL-33–TGF-b feedforward loop could potentially be exploited for cancer treatment.
UR - http://www.scopus.com/inward/record.url?scp=85088154965&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85088154965&partnerID=8YFLogxK
U2 - 10.1126/science.aay1813
DO - 10.1126/science.aay1813
M3 - Article
C2 - 32675345
AN - SCOPUS:85088154965
SN - 0036-8075
VL - 369
JO - Science
JF - Science
IS - 6501
M1 - eaay1813
ER -