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Hypoxic tumor microenvironment activates GLI2 via HIF-1{alpha} and TGF-{beta}2 to promote chemoresistance in colorectal cancer [Medical Sciences]

Colorectal cancer patients often relapse due to resistance to chemotherapy. The tumor microenvironment is known to contribute to tumor aggressiveness and chemoresistance, but the underlying mechanisms remain elusive. In the current study, we have shown that cancer-associated fibroblasts (CAFs) which are often present in the tumor can greatly promote resistance of colorectal cancer cells to chemotherapy. In the low-oxygen condition (hypoxia), CAFs-secreted growth factor TGF-β2 can induce strong expression of GLI2 , a gene that can induce resistance to therapy. As such, therapeutic targeting of TGF-β and GLI2 can be developed into a useful adjuvant to enhance the effect of chemotherapies.

Authors:   Yen-An Tang; Yu-feng Chen; Yi Bao; Sylvia Mahara; Siti Maryam J. M. Yatim; Gokce Oguz; Puay Leng Lee; Min Feng; Yu Cai; Ern Yu Tan; Sau Shung Fong; Zi-huan Yang; Ping Lan; Xiao-jian Wu; Qiang Yu
Journal:   Proceedings of the National Academy of Sciences current issue
Volume:   115
edition:   26
Year:   2018
Pages:   E5990
DOI:   10.1073/pnas.1801348115
Publication date:   26-Jun-2018
Facts, background information, dossiers
  • oxygen
  • hypoxia
  • Expression
More about Proceedings of the National Academy of Sciences
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