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Spleen tyrosine kinase SYK (L) interacts with YY 1 and coordinately suppresses SNAI 2 transcription in lung cancer cells
Author(s) -
Gao Dan,
Wang Lingling,
Zhang Hua,
Yan Xiaojie,
Yang Jie,
Zhou Ruimin,
Chang Xinzhong,
Sun Yanan,
Tian Shanshan,
Yao Zhi,
Zhang Kai,
Liu Zhe,
Ma Zhenyi
Publication year - 2018
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.14665
Subject(s) - syk , tyrosine kinase , chemistry , microbiology and biotechnology , transcription factor , biology , receptor , biochemistry , gene
Spleen tyrosine kinase ( SYK ) is a nonreceptor tyrosine kinase with dual properties of an oncoprotein and an oncosuppressor in distinctive cell types. In solid cancers, two isoforms SYK (L) and SYK (S) of SYK were recently identified due to its alternative mRNA splicing. However, the cellular activity and the biological significance of the long isoform of SYK , SYK (L), is still not well defined in human lung cancers. Here, we describe an interaction between SYK (L) and the ubiquitously expressed transcription regulator Yin Yang 1 ( YY 1) in the nucleus, which suppresses the epithelial‐to‐mesenchymal transition ( EMT ) by inactivating SNAI 2 (coding transcription factor SLUG ) transcription. Ch IP indicated that endogenous SYK (L) interacts directly with a YY 1 binding cis ‐regulatory element in the SNAI 2 promoter. Importantly, knockdown of YY 1 activates SYK (L)‐dependent EMT suppression in human lung cancer H1155 cells. We also found that the protein level of SYK (L) is markedly upregulated in various types of human lung cancers, and its nuclear localization is strongly correlated with clinical benefits of lung adenocarcinomas. Collectively, our data reveal a SYK (L)‐dependent transcriptional regulation of EMT through SLUG as a potential biomarker for lung cancer aggressiveness.