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SFMBT1 facilitates colon cancer cell metastasis and drug resistance combined with HMG20A

Ruijun Pan1,2, Dingye Yu1,2, Jiajia Hu3

  • 1Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Cell Death Discovery
|May 16, 2022
PubMed

Insights

Scm-like with four malignant brain tumor domains 1 (SFMBT1) is elevated in colorectal cancer (CRC) and drives resistance to 5-fluorouracil (5-FU). Targeting the SFMBT1/HMG20A axis may improve CRC treatment outcomes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Colorectal cancer (CRC) poses a significant health challenge, with drug resistance limiting treatment efficacy.
  • Scm-like with four malignant brain tumor domains 1 (SFMBT1) is increasingly recognized for its role in cancer progression.

Purpose of the Study:

  • To investigate the role of SFMBT1 in colorectal cancer drug resistance and metastasis.
  • To elucidate the molecular mechanism underlying SFMBT1-mediated chemoresistance, focusing on its interaction with HMG20A.

Main Methods:

  • Immunohistochemistry on CRC tissue microarrays to assess SFMBT1 expression.
  • In vitro assays (scratch, colony formation, Transwell) to evaluate SFMBT1's impact on CRC cell behavior.
  • Fluorescence co-localization and immunoprecipitation to determine SFMBT1-HMG20A interaction.
  • Murine xenograft and lung metastasis models for in vivo validation.

Main Results:

  • SFMBT1 expression is upregulated in CRC and significantly amplified in 5-fluorouracil (5-FU) resistant cells.
  • SFMBT1 promotes CRC proliferation, migration, invasion, and 5-FU resistance.
  • SFMBT1 directly interacts with high mobility group domain-containing protein 20A (HMG20A), and SFMBT1 depletion reduces HMG20A downstream signaling.
  • In vivo studies confirmed SFMBT1 and HMG20A's role in tumor growth and metastasis.

Conclusions:

  • The SFMBT1/HMG20A axis is a critical driver of 5-FU resistance and metastasis in colorectal cancer.
  • Targeting the SFMBT1/HMG20A pathway presents a potential therapeutic strategy to overcome chemoresistance and improve patient survival in CRC.

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