FER regulates endosomal recycling and is a predictor for adjuvant taxane benefit in breast cancer
Tavares, Sandra; Liv, Nalan; Pasolli, Milena; Opdam, Mark; Rätze, Max A K; Saornil, Manuel; Sluimer, Lilian M; Hengeveld, Rutger C C; van Es, Robert; van Werkhoven, Erik; Vos, Harmjan; Rehmann, Holger; Burgering, Boudewijn M T; Oosterkamp, Hendrika M; Lens, Susanne M A; Klumperman, Judith; Linn, Sabine C; Derksen, Patrick W B
(2022) Cell Reports, volume 39, issue 1, pp. 1 - 24
(Article)
Abstract
Elevated expression of non-receptor tyrosine kinase FER is an independent prognosticator that correlates with poor survival of high-grade and basal/triple-negative breast cancer (TNBC) patients. Here, we show that high FER levels are also associated with improved outcomes after adjuvant taxane-based combination chemotherapy in high-risk, HER2-negative patients. In TNBC cells, we
... read more
observe a causal relation between high FER levels and sensitivity to taxanes. Proteomics and mechanistic studies demonstrate that FER regulates endosomal recycling, a microtubule-dependent process that underpins breast cancer cell invasion. Using chemical genetics, we identify DCTN2 as a FER substrate. Our work indicates that the DCTN2 tyrosine 6 is essential for the development of tubular recycling domains in early endosomes and subsequent propagation of TNBC cell invasion in 3D. In conclusion, we show that high FER expression promotes endosomal recycling and represents a candidate predictive marker for the benefit of adjuvant taxane-containing chemotherapy in high-risk patients, including TNBC patients.
show less
Download/Full Text
Keywords: Breast Neoplasms/metabolism, Bridged-Ring Compounds/pharmacology, Endosomes/metabolism, Female, Humans, Taxoids/pharmacology, Triple Negative Breast Neoplasms/drug therapy, endosomal recycling, taxanes, breast cancer, DCNT2, FER, analog sensitive, metastasis, dynamitin, dynactin, General Biochemistry,Genetics and Molecular Biology, Journal Article
ISSN: 2211-1247
Publisher: Cell Press
Note: Publisher Copyright: © 2022 The Authors
(Peer reviewed)