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SMYD2-OE promotes oxaliplatin resistance in colon cancer through MDR1/P-glycoprotein via MEK/ERK/AP1 pathway

Hailiang Ren1, Zheng Wang2, Yao Chen3

  • 1Department of General Surgery, The Third People's Hospital of Chengdu, The Second Affiliated Hospital of Chengdu, Chongqing Medical University, Sichuan, P.R. China, yuntaodrli@126.com.

Oncotargets and Therapy
|May 2, 2019
PubMed
Abstract

Insights

SET and MYND domain-containing protein 2 (SMYD2-OE) overexpression promotes oxaliplatin resistance in colon cancer by upregulating MDR1/P-glycoprotein. Knocking down SMYD2-OE may sensitize colon cancer to chemotherapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • SET and MYND domain-containing protein 2 (SMYD2-OE) is implicated in cancer development.
  • The role of SMYD2-OE in colon cancer and its link to oxaliplatin (L-OHP) resistance are poorly understood.
  • Oxaliplatin resistance is a major challenge in colon cancer chemotherapy.

Purpose of the Study:

  • To investigate the expression of SMYD2-OE in colon cancer tissues.
  • To explore the relationship between SMYD2-OE and L-OHP resistance in colon cancer.
  • To elucidate the underlying molecular mechanism of SMYD2-OE in mediating L-OHP resistance.

Main Methods:

  • Analysis of SMYD2-OE expression in patient-derived colon cancer tissues.
  • In vitro and in vivo experiments to assess the functional role of SMYD2-OE in colon cancer cell sensitivity to L-OHP.
  • Investigation of the MEK/ERK/AP-1 signaling pathway and MDR1/P-glycoprotein expression.

Main Results:

  • SMYD2-OE was overexpressed in colon cancer tissues and correlated with poor prognosis after L-OHP chemotherapy.
  • SMYD2-OE knockdown enhanced colon cancer sensitivity to L-OHP in vitro and in vivo.
  • SMYD2-OE overexpression conferred L-OHP resistance by upregulating MDR1/P-glycoprotein via the MEK/ERK/AP-1 pathway.

Conclusions:

  • SMYD2-OE promotes L-OHP resistance in colon cancer by modulating MDR1/P-glycoprotein through the MEK/ERK/AP-1 signaling pathway.
  • SMYD2-OE represents a potential therapeutic target to overcome L-OHP resistance in colon cancer.
  • SMYD2-OE knockdown offers a promising strategy to sensitize colon cancer to chemotherapy.
Keywords:
MEK/ERK/AP-1 signaling pathwaySMYD2-OEcolon canceroxaliplatin resistance

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