Par-4 downregulation promotes breast cancer recurrence by preventing multinucleation following targeted therapy.

Journal Article

Most deaths from breast cancer result from tumor recurrence, but mechanisms underlying tumor relapse are largely unknown. We now report that Par-4 is downregulated during tumor recurrence and that Par-4 downregulation is necessary and sufficient to promote recurrence. Tumor cells with low Par-4 expression survive therapy by evading a program of Par-4-dependent multinucleation and apoptosis that is otherwise engaged following treatment. Low Par-4 expression is associated with poor response to neoadjuvant chemotherapy and an increased risk of relapse in patients with breast cancer, and Par-4 is downregulated in residual tumor cells that survive neoadjuvant chemotherapy. Our findings identify Par-4-induced multinucleation as a mechanism of cell death in oncogene-addicted cells and establish Par-4 as a negative regulator of breast cancer recurrence.

Full Text

Duke Authors

Cited Authors

  • Alvarez, JV; Pan, T-C; Ruth, J; Feng, Y; Zhou, A; Pant, D; Grimley, JS; Wandless, TJ; Demichele, A; I-SPY 1 TRIAL Investigators, ; Chodosh, LA

Published Date

  • July 2013

Published In

Volume / Issue

  • 24 / 1

Start / End Page

  • 30 - 44

PubMed ID

  • 23770012

Electronic International Standard Serial Number (EISSN)

  • 1878-3686

International Standard Serial Number (ISSN)

  • 1535-6108

Digital Object Identifier (DOI)

  • 10.1016/j.ccr.2013.05.007

Language

  • eng