Targeting Hypoxia-Inducible Factor-1-Mediated Metastasis for Cancer Therapy.

Abstract

Significance: Hypoxia is emerging as a crucial regulator of the tumor microenvironment; it governs the metastatic potential of multiple primary cancers. It is also potentially involved in the regulation of tumorigenesis, tumor metabolism, and proangiogenic activity. Recent Advances: A wealth of clinical data across a wide range of cancer types has revealed strong correlations between hypoxia or the overexpression of hypoxia-inducible transcription factors and the rates of distant metastases and poor prognoses. Hypoxia-inducible factor (HIF)-1α, one of the key regulatory molecules of the HIF-1 signaling pathways, is involved in multiple crucial steps in the metastatic cascade. Critical Issues: Here, we present recent findings on the roles of the HIF-1 complex in tumor metastasis and highlight the potential of HIF-1α as a target for abrogating tumor metastasis. Moreover, we systematically describe the regulatory role of HIF-1 at each step of the metastatic cascade. Finally, we present the most recent advances in potential pharmacological interventions and the development of specific HIF-1 inhibitors for blocking tumor metastasis. Future Directions: Well-designed clinical trials are urgently needed to validate the anti-metastatic activity of HIF-1 inhibitors discovered in preclinical models. Antioxid. Redox Signal. 34, 1484-1497.

• Authors: Zhaowu Ma, Louis Zizhao Wang, Jun-Ting Cheng, Walter Sze Tung Lam, Xiang Ma, Xiaoqiang Xiang, Andrea Li-Ann Wong, Boon Cher Goh, Quan Gong, Gautam Sethi, Lingzhi Wang
• Journal: Antioxidants & redox signaling (Antioxid Redox Signal) Vol. 34 Issue 18 Pg. 1484-1497 (06 20 2021) ISSN: 1557-7716 [Electronic] United States
• PMID: 33198508 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Antineoplastic Agents
• HIF1A protein, human
• Hypoxia-Inducible Factor 1, alpha Subunit

Topics

• Antineoplastic Agents (pharmacology, therapeutic use)
• Cell Movement (drug effects)
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Hypoxia-Inducible Factor 1, alpha Subunit (genetics, metabolism)
• Neoplasm Metastasis (drug therapy, genetics)
• Prognosis
• Signal Transduction (drug effects)
• Tumor Hypoxia (drug effects)
• Tumor Microenvironment (drug effects)