TY - JOUR
T1 - Notch1 pathway activity determines the regulatory role of cancer-associated fibroblasts in melanoma growth and invasion
AU - Shao, Hongwei
AU - Kong, Ranran
AU - Ferrari, Massimiliano L.
AU - Radtke, Freddy
AU - Capobianco, Anthony J.
AU - Liu, Zhao Jun
N1 - Funding Information:
This study was supported by Bankhead-Coley Cancer Research Program (Award# 09BN-11), Women''s Cancer Association and internal funds from the University of Miami to Z. Liu. We thank Dr. Omaida C. Velazquez (University of Miami) for helpful collaborations, consultation and discussions.
Publisher Copyright:
© 2015 Shao et al.This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2015/11/1
Y1 - 2015/11/1
N2 - Cancer-associated fibroblasts (CAF) play a crucial role in regulating cancer progression, yet the molecular determinant that governs the tumor regulatory role of CAF remains unknown. Using a mouse melanoma model in which exogenous melanoma cells were grafted on the skin of two lines of mice where the genetic activation or inactivation of Notch1 signaling specifically occurs in natural host stromal fibroblasts, we demonstrated that Notch1 pathway activity could determine the tumor-promoting or tumor-suppressing phenotype in CAF. CAF carrying elevated Notch1 activity significantly inhibited melanoma growth and invasion, while those with a null Notch1 promoted melanoma invasion. These findings identify the Notch1 pathway as a molecular determinant that controls the regulatory role of CAF in melanoma skin growth and invasion, unveiling Notch1 signaling as a potential therapeutic target for melanoma and potentially other solid tumors.
AB - Cancer-associated fibroblasts (CAF) play a crucial role in regulating cancer progression, yet the molecular determinant that governs the tumor regulatory role of CAF remains unknown. Using a mouse melanoma model in which exogenous melanoma cells were grafted on the skin of two lines of mice where the genetic activation or inactivation of Notch1 signaling specifically occurs in natural host stromal fibroblasts, we demonstrated that Notch1 pathway activity could determine the tumor-promoting or tumor-suppressing phenotype in CAF. CAF carrying elevated Notch1 activity significantly inhibited melanoma growth and invasion, while those with a null Notch1 promoted melanoma invasion. These findings identify the Notch1 pathway as a molecular determinant that controls the regulatory role of CAF in melanoma skin growth and invasion, unveiling Notch1 signaling as a potential therapeutic target for melanoma and potentially other solid tumors.
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U2 - 10.1371/journal.pone.0142815
DO - 10.1371/journal.pone.0142815
M3 - Article
C2 - 26562315
AN - SCOPUS:84955446926
VL - 10
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 11
M1 - e0142815
ER -