Proteomics of cancer cell lines resistant to microtubule-stabilizing agents

Jakob Albrethsen1, Ruth H Angeletti, Susan Band Horwitz

  • 1Corresponding Author: Chia-Ping Huang Yang, Department of Molecular Pharmacology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461. chia-ping.h.yang@einstein.yu.edu.

Insights

Predicting patient response to microtubule-stabilizing agents (MSAs) is challenging. This study identified galectin-1 as a potential biomarker for MSA resistance in cancer cells, showing its suppression increases drug sensitivity.

Area of Science:

  • Oncology
  • Proteomics
  • Molecular Biology

Background:

  • Microtubule-interacting agents (MIAs) are clinically successful cancer drugs.
  • Predicting individual patient response to MIAs remains a significant challenge for oncologists.

Purpose of the Study:

  • To investigate cellular resistance mechanisms to microtubule-stabilizing agents (MSAs) using proteomics.
  • To identify potential predictive biomarkers for MSA response.

Main Methods:

  • Comparative proteomics using 2D DIGE on six cell lines, including drug-sensitive and drug-resistant cancer cell lines (lung and ovarian).
  • Validation of proteomic findings using Western blot analyses.
  • Investigated the role of galectin-1 in drug resistance and sensitivity.

Main Results:

  • Differential expression of cytoskeletal and associated proteins was observed in drug-resistant cells.
  • Galectin-1 was significantly increased in epothilone B (EpoB)- and ixabepilone-resistant cells.
  • Suppression of galectin-1 enhanced drug sensitivity in both sensitive and resistant ovarian cancer cells, with elevated galectin-1 found in the medium of resistant cells.

Conclusions:

  • Galectin-1 is a promising candidate predictive biomarker for microtubule-stabilizing agent (MSA) resistance.
  • Galectin-1 may play a direct role in mediating resistance to MSAs.
  • Further studies on galectin-1, 14-3-3σ, and stathmin phosphorylation are warranted for biomarker development.

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