Dual Mechanisms of LYN Kinase Dysregulation Drive Aggressive Behavior in Breast Cancer Cells

Giusy Tornillo, Catherine Knowlson, Howard Kendrick, Joe Cooke, Hasan Mirza, Iskander Aurrekoetxea-Rodríguez, Maria D M Vivanco, Niamh E Buckley, Anita Grigoriadis, Matthew J Smalley

Research output: Contribution to journalArticlepeer-review


The SRC-family kinase LYN is highly expressed in triple-negative/basal-like breast cancer (TNBC) and in the cell of origin of these tumors, c-KIT-positive luminal progenitors. Here, we demonstrate LYN is a downstream effector of c-KIT in normal mammary cells and protective of apoptosis upon genotoxic stress. LYN activity is modulated by PIN1, a prolyl isomerase, and in BRCA1 mutant TNBC PIN1 upregulation activates LYN independently of c-KIT. Furthermore, the full-length LYN splice isoform (as opposed to the Δaa25-45 variant) drives migration and invasion of aggressive TNBC cells, while the ratio of splice variants is informative for breast cancer-specific survival across all breast cancers. Thus, dual mechanisms-uncoupling from upstream signals and splice isoform ratios-drive the activity of LYN in aggressive breast cancers.

Original languageEnglish
Pages (from-to)3674-3692.e10
Number of pages19
JournalCell reports
Issue number13
Publication statusPublished - 26 Dec 2018

Bibliographical note

Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.


  • Adolescent
  • Adult
  • Animals
  • BRCA1 Protein/deficiency
  • Breast Neoplasms/enzymology
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Epithelial Cells/metabolism
  • Female
  • Gene Expression Regulation, Neoplastic
  • HEK293 Cells
  • Humans
  • Isoenzymes/metabolism
  • Mice
  • NIMA-Interacting Peptidylprolyl Isomerase/metabolism
  • Neoplasm Invasiveness
  • Proto-Oncogene Proteins c-kit/metabolism
  • RNA Splicing/genetics
  • Survival Analysis
  • Up-Regulation
  • Young Adult
  • src-Family Kinases/genetics

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