FYN promotes mesenchymal phenotypes of basal type breast cancer cells through STAT5/NOTCH2 signaling node.

Abstract:

:Basal type breast cancer is the most aggressive and has mesenchymal features with a high metastatic ability. However, the signaling node that determines the basal type features in breast cancer remains obscure. Here, we report that FYN among SRC family kinases is required for the maintenance of basal type breast cancer subtype. Importantly, FYN enhanced NOTCH2 activation in basal type breast cancer cells through STAT5-mediated upregulation of Jagged-1 and DLL4 NOTCH ligands, thereby contributed to mesenchymal phenotypes. In addition, we found that high levels of FYN persist in basal type breast cancer cells by a positive feedback loop between FYN and STAT5. FYN interacted directly with STAT5 and increased p-STAT5 that further acts as a transcription factor for FYN. Taken together, our findings demonstrate a pivotal role of FYN and its downstream effectors in maintaining the basal type features in breast cancer.

journal_name

Oncogene

journal_title

Oncogene

authors

Lee GH,Yoo KC,An Y,Lee HJ,Lee M,Uddin N,Kim MJ,Kim IG,Suh Y,Lee SJ

doi

10.1038/s41388-017-0114-y

subject

Has Abstract

pub_date

2018-04-01 00:00:00

pages

1857-1868

issue

14

eissn

0950-9232

issn

1476-5594

pii

10.1038/s41388-017-0114-y

journal_volume

37

pub_type

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