Tornillo, Giusy, Knowlson, Catherine, Kendrick, Howard, Cooke, Joe, Mirza, Hasan, Aurrekoetxea-Rodriguez, Iskander, d.M. Vivanco, Maria, Buckley, Niamh E., Grigoriadis, Anita and Smalley, Matthew J.  ORCID: https://orcid.org/0000-0001-9540-1146
2018.
Dual mechanisms of LYN kinase dysregulation drive aggressive behaviour in breast cancer cells.
Cell Reports
25
(13)
, pp. 3674-3692.
10.1016/j.celrep.2018.11.103
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Abstract
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.
| Item Type: | Article |
|---|---|
| Date Type: | Publication |
| Status: | Published |
| Schools: | Schools > Biosciences Research Institutes & Centres > European Cancer Stem Cell Research Institute (ECSCRI) |
| Additional Information: | This is an open access article under the terms of the CC-BY Attribution 4.0 International license. |
| Publisher: | Elsevier |
| ISSN: | 2211-1247 |
| Funders: | Cancer Research UK |
| Date of First Compliant Deposit: | 21 November 2018 |
| Date of Acceptance: | 29 November 2018 |
| Last Modified: | 04 May 2023 05:55 |
| URI: | https://orca.cardiff.ac.uk/id/eprint/116972 |
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