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SUMOylated hnRNPM suppresses PFKFB3 phosphorylation to regulate glycolysis and tumorigenesis

Ya-Xian Zhong1, Huan-Bin Zhao2, Meng-Han Lian3

  • 1Institute of Aging & Tissue Regeneration, Stress and Cancer Research Unit of Chinese Academy of Medical Sciences (No. 2019RU043), State Key Laboratory of Systems Medicine for Cancer, Ren-Ji Hospital, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, 200127, China; Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, SJTU-SM, Shanghai, 200025, China.

Cancer Letters
|February 21, 2025
PubMed

Insights

SUMOylation of heterogeneous nuclear ribonucleoprotein M (hnRNPM) regulates colorectal cancer by inhibiting glycolysis and lactate production. This novel mechanism impacts tumor growth and offers new therapeutic targets.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Heterogeneous nuclear ribonucleoprotein M (hnRNPM) is a splicing factor involved in cancer, but its precise mechanisms are unclear.
  • Previous research focused on hnRNPM's RNA-binding and splicing roles.

Purpose of the Study:

  • To investigate the non-splicing roles of hnRNPM in colorectal cancer.
  • To identify post-translational modifications of hnRNPM in colorectal cancer cells.

Main Methods:

  • Global SUMOylated proteomic screening in colorectal cancer cells.
  • Interaction studies between hnRNPM, SENP1, and PFKFB3.
  • In vivo tumorigenesis assays in mice.
  • Analysis of patient samples for hnRNPM SUMOylation and related protein levels.

Main Results:

  • hnRNPM is SUMOylated at lysine 17, and SENP1 mediates its de-SUMOylation.
  • hnRNPM SUMOylation inhibits glycolysis by interacting with PFKFB3, affecting its localization and phosphorylation, thereby suppressing lactate production.
  • SUMO-deficient hnRNPM promotes colorectal cancer cell proliferation and tumorigenesis in mice.
  • A negative correlation exists between hnRNPM SUMOylation and SENP1 expression or phosphorylated PFKFB3 levels in colorectal cancer patient samples.

Conclusions:

  • hnRNPM SUMOylation plays a critical role in regulating colorectal cancer cell metabolism and growth independent of its splicing functions.
  • Modulating hnRNPM SUMOylation presents a potential therapeutic strategy for colorectal cancer.
Keywords:
Colorectal cancer cellsGlycolysisPFKFB3SUMOylationhnRNPM

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