Enriched variations in TEKT4 and breast cancer resistance to paclitaxel

Nat Commun. 2014 May 13;5:3802. doi: 10.1038/ncomms4802.


Among chemotherapeutic agents, paclitaxel has shown great efficacy against breast cancer. Prediction of paclitaxel response may improve patient outcomes. Here we show, using exome sequencing, that in comparison with pre-treatment biopsies, two TEKT4 germline variations are enriched in post-treatment tumours. We find TEKT4 variations in ~ 10% of an independent cohort of 84 pairs of samples. Tektin4 (encoded by TEKT4) associates closely with tubulin in doublet microtubules and helps stabilize these structures. These two TEKT4 germline variations in a high cis linkage are biologically relevant, as the ectopic expression of variant TEKT4 deregulates the microtubule stability, antagonizes the paclitaxel-induced stabilizing effect of microtubules and increases paclitaxel resistance. Furthermore, TEKT4 germline variations are associated with reduced disease-free survival and overall survival compared with wild-type TEKT4 in patients undergoing paclitaxel-based chemotherapy. Taken together, we reveal a potential mechanism of resistance to paclitaxel through the acquisition of germline variations in breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antineoplastic Agents, Phytogenic / therapeutic use*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics*
  • Carcinoma, Ductal, Breast / drug therapy
  • Carcinoma, Ductal, Breast / genetics*
  • Cell Line, Tumor
  • Cohort Studies
  • Drug Resistance, Neoplasm / genetics*
  • Female
  • Genetic Variation
  • Humans
  • Microtubule Proteins / genetics*
  • Microtubules / metabolism*
  • Middle Aged
  • Paclitaxel / therapeutic use*
  • Prognosis


  • Antineoplastic Agents, Phytogenic
  • Microtubule Proteins
  • tektins
  • Paclitaxel