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DAB2IP inhibits glucose uptake by modulating HIF-1α ubiquitination under hypoxia in breast cancer

Hongliang Dong1,2, Weiyi Jia1,2,3, Weijian Meng1,2

  • 1Department of GI Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

Oncogenesis
|June 11, 2024
PubMed

Insights

DAB2IP suppresses glucose uptake in breast cancer by inhibiting HIF-1α signaling. It achieves this by interacting with STUB1, leading to HIF-1α degradation and reduced tumor progression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Metabolism

Background:

  • Metabolic reprogramming is crucial in tumor biology, with glucose metabolism frequently altered in breast cancer.
  • DAB2IP is a known tumor suppressor in breast cancer, but its role in regulating glucose uptake is not fully understood.

Purpose of the Study:

  • To investigate the mechanism by which DAB2IP regulates glucose uptake in breast cancer cells.
  • To elucidate the role of DAB2IP in hypoxia-driven metabolic changes and tumor progression.

Main Methods:

  • Investigated DAB2IP's effect on glucose uptake in breast cancer cells under hypoxia.
  • Utilized co-immunoprecipitation to study protein interactions between DAB2IP, STUB1, and HIF-1α.
  • Assessed HIF-1α ubiquitylation and degradation.
  • Examined the impact of DAB2IP's PER domain deletion on cellular metabolism.

Main Results:

  • DAB2IP inhibited glucose uptake in breast cancer cells under hypoxia by suppressing HIF-1α signaling.
  • DAB2IP interacted with STUB1 via its PER domain, promoting HIF-1α ubiquitylation and degradation.
  • Deletion of the PER domain abolished DAB2IP's inhibitory effects on glucose uptake, ATP, and lactic acid production.

Conclusions:

  • DAB2IP plays a significant role in regulating cancer-related glucose metabolism.
  • A novel mechanism involving STUB1-mediated HIF-1α degradation regulated by DAB2IP was identified in breast cancer.

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