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SRPK1/AKT axis promotes oxaliplatin-induced anti-apoptosis via NF-κB activation in colon cancer

Jing-Qiang Huang1, He-Feng Li1,2, Jing Zhu1

  • 1Guangdong Key Laboratory for Genome Stability and Human Disease Prevention, Department of Biochemistry and Molecular Biology, Health Science Center, Shenzhen University, Shenzhen, Guangdong, 518060, P. R. China.

Journal of Translational Medicine
|July 1, 2021
PubMed
Abstract

Insights

The study reveals that SRPK1 promotes colon cancer progression and oxaliplatin resistance by enhancing anti-apoptosis via NF-κB pathway activation. This suggests SRPK1 as a potential therapeutic target for colon cancer treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • Colorectal cancer is a common diagnosis, with oxaliplatin as a primary treatment.
  • Oxaliplatin resistance significantly limits treatment efficacy.
  • The role of SRPK1 in mediating drug resistance in colon cancer remains unclear.

Purpose of the Study:

  • To investigate the role of SRPK1 in colon cancer progression and oxaliplatin resistance.
  • To elucidate the underlying molecular mechanisms, including its involvement in apoptosis and the NF-κB pathway.
  • To evaluate SRPK1 as a potential therapeutic target for colon cancer.

Main Methods:

  • Analyzed SRPK1 expression in pan-cancer datasets (TCGA, CPTAC) and colon cancer tissues/cell lines (IHC, western blot).
  • Assessed anti-apoptosis using MTT and TUNEL assays.
  • Investigated NF-κB pathway activation via luciferase assay and qRT-PCR, examining key protein phosphorylation levels (AKT, IKK, IκB).

Main Results:

  • SRPK1 expression is elevated in colon cancer tissues and associated with advanced clinical stage and poor prognosis.
  • SRPK1 overexpression enhances colon cancer cell survival under oxaliplatin treatment, while silencing reduces it.
  • SRPK1 promotes oxaliplatin resistance by activating the NF-κB pathway through IKK and IκB phosphorylation, facilitating nuclear translocation.

Conclusions:

  • SRPK1 plays a crucial role in colon cancer progression and confers oxaliplatin resistance.
  • SRPK1 enhances cancer cell survival via NF-κB pathway activation.
  • SRPK1 represents a promising therapeutic target for overcoming oxaliplatin resistance in colon cancer.
Keywords:
Anti-apoptosisColon cancerNF-κB activationOxaliplatin resistanceSRPK1

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