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REVIEW article

Front. Oncol.
Sec. Cancer Molecular Targets and Therapeutics
Volume 14 - 2024 | doi: 10.3389/fonc.2024.1484515

Targeting the SMURF2-HIF1α Axis: A New Frontier in Cancer Therapy

Provisionally accepted
Emile Youssef Emile Youssef 1*Shuai Zhao Shuai Zhao 2Connor Purcell Connor Purcell 2*Gary L. Olson Gary L. Olson 3Wafik El-Deiry Wafik El-Deiry 4*
  • 1 Smurf-Therapeutics, Providence, United States
  • 2 Brown University, Providence, Rhode Island, United States
  • 3 Provid Pharmaceuticals, Inc.,, Monmouth Junction, United States
  • 4 Warren Alpert Medical School, Brown University, Providence, Rhode Island, United States

The final, formatted version of the article will be published soon.

    The interaction between SMAD-specific E3 ubiquitin protein ligase 2 (SMURF2) and Hypoxia-Inducible Factor 1-alpha (HIF1α) plays a pivotal role in modulating the cellular response to hypoxic conditions within the tumor microenvironment (TME). SMURF2, acting as a tumor suppressor, targets HIF1α for ubiquitination and subsequent proteasomal degradation via the Ubiquitin-Proteasome System (UPS), thereby inhibiting pathways that facilitate cancer cell survival, proliferation, and angiogenesis. The Autophagy-Lysosome Pathway (ALP) also contributes to the degradation of cellular components, complementing the UPS in maintaining protein homeostasis under stress conditions. This review examines the critical impact of SMURF2 on tumorigenesis through its regulation of HIF1α stability, emphasizing its potential as a therapeutic target.

    Keywords: Smurf2, HIF1α, Tumor Microenvironment, metabolic reprogramming, ferroptosis, ubiquitin-proteasome system, Cellular adaptation

    Received: 22 Aug 2024; Accepted: 29 Aug 2024.

    Copyright: © 2024 Youssef, Zhao, Purcell, Olson and El-Deiry. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Emile Youssef, Smurf-Therapeutics, Providence, United States
    Connor Purcell, Brown University, Providence, 02912, Rhode Island, United States
    Wafik El-Deiry, Warren Alpert Medical School, Brown University, Providence, 02912, Rhode Island, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.