Related Experiment Video

Updated: Feb 1, 2026

Orthotopic Mouse Model of Colorectal Cancer
08:43

Orthotopic Mouse Model of Colorectal Cancer

Published on: December 4, 2007

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MYLK4 promotes colorectal cancer progression by regulating lipid metabolism reprogramming via targeting ferroptosis

Bishi Wang1, Kongxiu Wu1, Xin Liu1

  • 1Department of Gastrointestinal Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250117, China.

Neoplasia (New York, N.Y.)
|January 30, 2026
PubMed

Insights

Myosin light chain kinase 4 (MYLK4) drives colorectal cancer (CRC) resistance to tyrosine kinase inhibitors (TKIs) by altering lipid metabolism. Targeting MYLK4 and stearoyl-CoA desaturase 1 (SCD1) shows promise for treating resistant CRC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Colorectal cancer (CRC) pathophysiology is complex, hindering novel pharmaceutical development.
  • Drug resistance, particularly to tyrosine kinase inhibitors (TKIs), limits advanced CRC treatment efficacy.

Purpose of the Study:

  • To investigate the role of myosin light chain kinase family member 4 (MYLK4) in TKI resistance in CRC.
  • To elucidate the mechanisms underlying MYLK4-mediated drug resistance and identify potential therapeutic targets.

Main Methods:

  • Investigated MYLK4 interaction with MDM2 and TRIM15 to affect p53.
  • Analyzed the p53-SCD1 regulatory axis in CRC.
  • Evaluated the efficacy of combined regorafenib and SCD1 inhibitor-3 treatment in CRC models.

Main Results:

  • MYLK4 promotes TKI resistance in CRC via lipid metabolic reprogramming.
  • MYLK4 enhances p53 degradation through MDM2-TRIM15 interaction, leading to increased stearoyl-CoA desaturase 1 (SCD1) expression.
  • Elevated MYLK4 and SCD1 levels correlate with regorafenib resistance and poor prognosis in CRC patients.
  • Co-treatment with regorafenib and an SCD1 inhibitor demonstrated significant anti-tumor effects in preclinical models.

Conclusions:

  • MYLK4-driven lipid metabolism reprogramming confers TKI resistance in colorectal cancer.
  • Combined inhibition of MYLK4 and SCD1 presents a potential therapeutic strategy for TKI-resistant CRC, especially in patients with wild-type p53.
Keywords:
Colorectal cancerFerroptosisMYLK4RegorafenibTRIM15

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