当前位置： SCI文献检索 > CELLULAR SIGNALLING期刊下所有文献 > Lysophosphatidic acid induces integrin β6 expression in human oral squamous cell carcinomas cells via LPAR1 coupling to Gαi and downstream SMAD3 and ETS-1 activation.

Lysophosphatidic acid induces integrin β6 expression in human oral squamous cell carcinomas cells via LPAR1 coupling to Gαi and downstream SMAD3 and ETS-1 activation.

Abstract：

:Integrin β6 (ITGB6), an epithelial-specific integrin, is upregulated in oral squamous cell carcinomas (OSCC) and is associated with progression and metastasis of OSCC. Lysophosphatidic acid (LPA), an important bioactive phospholipid present in saliva, has also been related to OSCC cell migration and invasiveness. LPA exerts its biological effects through signal transduction pathways that ultimately regulate gene expression. However, it is unclear whether LPA signaling is involved in ITGB6 upregulation in OSCC. Therefore, the aim of the current study was to investigate the role of LPA in the regulation of ITGB6 expression in OSCC cells, and to delineate the molecular signaling pathways involved. Using SAS and HSC-3 OSCC cell lines, we found that LPA increases ITGB6 mRNA expression without affecting mRNA stability, suggesting that LPA acts by regulating ITGB6 gene transcription. In addition, we show that LPA stimulation increases phosphorylation and binding of the transcription factors SMAD3 and ETS-1 to the ITGB6 promoter resulting in ITGB6 active transcription. Finally, we demonstrate that LPA-induced ITGB6 expression is mediated via the LPA receptors 1 (LPAR1) coupling to Gαi. Our findings provide insights into the molecular mechanism underlying ITGB6 overexpression in OSCC and may have important implications for therapeutic purposes.

journal_name

Cell Signal

journal_title

Cellular signalling

authors

Xu M,Yin H,Cai Y,Huang W,Ji Q,Liu F,Shi S,Deng X

doi

10.1016/j.cellsig.2019.04.008

subject

Has Abstract

pub_date

2019-08-01 00:00:00

pages

81-90

eissn

0898-6568

issn

1873-3913

pii

S0898-6568(19)30084-1

journal_volume

60

pub_type

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