Open AccessCompression-induced expression of glycolysis genes in CAFs correlates with EMT and angiogenesis gene expression in breast cancer
Author(s) -
Baek Gil Kim,
Jin Sol Sung,
Yeonsue Jang,
Yoon Jin,
Suki Kang,
Hyunho Han,
Juhyun Lee,
Nam Hoon Cho
Publication year - 2019
Publication title -
communications biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.812
H-Index - 26
ISSN - 2399-3642
DOI - 10.1038/s42003-019-0553-9
Subject(s) - angiogenesis , stromal cell , cancer research , breast cancer , metastasis , cancer cell , biology , gene expression , fibroblast growth factor , cancer , tumor progression , gene , genetics , receptor
Tumor growth increases compressive stress within a tissue, which is associated with solid tumor progression. However, very little is known about how compressive stress contributes to tumor progression. Here, we show that compressive stress induces glycolysis in human breast cancer associated fibroblast (CAF) cells and thereby contributes to the expression of epithelial to mesenchymal (EMT)- and angiogenesis-related genes in breast cancer cells. Lactate production was increased in compressed CAF cells, in a manner dependent on the expression of metabolic genes ENO2 , HK2 , and PFKFB3 . Conditioned medium from compressed CAFs promoted the proliferation of breast cancer cells and the expression of EMT and/or angiogenesis-related genes. In patient tissues with high compressive stress, the expression of compression-induced metabolic genes was significantly and positively correlated with EMT and/or angiogenesis-related gene expression and metastasis size. These findings illustrate a mechanotransduction pathway involving stromal glycolysis that may be relevant also for other solid tumours.