Solid cancers are composed of malignant cells and their surrounding matrix components. Hypoxia plays a critical role in shaping the tumor microenvironment that contributes to cancer progression and treatment failure. Cancer-associated fibroblasts (CAFs) are one of the most prominent components of the tumor microenvironment. CAFs are highly sensitive to hypoxia and participates in the crosstalk with cancer cells. Hypoxic CAFs modulate several mechanisms that induce cancer malignancy, such as extracellular matrix (ECM) remodeling, immune evasion, metabolic reprogramming, angiogenesis, metastasis, and drug resistance. Key signaling molecules regulating CAFs in hypoxia include transforming growth factor (TGF-β) and hypoxia-inducible factors (HIFs). In this article, we summarize the mechanisms underlying the hypoxic regulation of CAFs and how hypoxic CAFs affect cancer development and progression. We also discuss the potential therapeutic strategies focused on targeting CAFs in the hypoxic tumor microenvironment.
Bibliographical noteFunding Information:
This research was funded by the National Research Foundation of Korea (NRF-2021R1C1C 2004561, NRF-2021R1A5A2031612); the Inha University Research Grant; and the National R&D Program for Cancer Control, Ministry of Health and Welfare, Republic of Korea.
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
- cancer-associated fibroblast
- tumor microenvironment
ASJC Scopus subject areas
- Cancer Research