NDLI: Overexpression of CASS4 promotes invasion in non-small cell lung cancer by activating the AKT signaling pathway and inhibiting E-cadherin expression

Content Provider	Springer Nature Link
Author	Li, Ailin Zhang, Weiwei Xia, Huifang Miao, Yuan Zhou, Haijing Zhang, Xiupeng Dong, Qianze Li, Qingchang Qiu, Xueshan Wang, Enhua
Copyright Year	2016
Abstract	The role of Crk-associated substrate (CAS) family members in regulating invasion and metastasis has been described in several cancers. As the fourth member of the CAS family, CASS4 is also related with positive lymph node metastasis and poor prognosis in lung cancer. However, the underlying mechanisms and downstream effectors of CASS4 in the development and progression of non-small cell lung cancer (NSCLC) remain unclear. In this study, CASS4 overexpression inhibited E-cadherin expression and enhanced invasion in NSCLC cell line transfected with CASS4 plasmid, while CASS4 depletion upregulated E-cadherin expression and inhibited invasion in NSCLC cell line transfected with CASS4 siRNA. The effect of CASS4 overexpression in facilitating invasion of NSCLC cells was reversed by restoring E-cadherin expression, which indicates that CASS4 may promote invasion by inhibiting E-cadherin expression. Subsequent immunohistochemistry results confirmed that CASS4 overexpression correlated with loss of E-cadherin expression. We next investigated the phosphorylation levels of focal adhesion kinase (FAK), p38, extracellular signal-related kinase (ERK), and AKT after CASS4 plasmid or CASS4 siRNA transfection. CASS4 facilitated AKT (Ser473) phosphorylation. Treatment with an AKT phosphorylation inhibitor reversed the increased invasive capacity and downregulation of E-cadherin protein induced by CASS4 overexpression. Taken together, the present results indicate that CASS4 may promote NSCLC invasion by activating the AKT signaling pathway, thereby inhibiting E-cadherin expression.
Starting Page	15157
Ending Page	15164
Page Count	8
File Format	PDF
ISSN	10104283
Journal	Tumor Biology
Volume Number	37
Issue Number	11
e-ISSN	14230380
Language	English
Publisher	Springer Netherlands
Publisher Date	2016-09-27
Publisher Place	Dordrecht
Access Restriction	Subscribed
Subject Keyword	CASS4 AKT E-cadherin Non-small cell lung cancer Invasion Cancer Research
Content Type	Text
Resource Type	Article
Subject	Medicine Cancer Research

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