Overexpression of CASS4 promotes invasion in non-small cell lung cancer by activating the AKT signaling pathway and inhibiting E-cadherin expression.
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.
Department of Radiotherapy, The First Affiliated Hospital of China Medical University, Shenyang, China.
Ailin
A
Li
Department of Radiotherapy, The First Affiliated Hospital of China Medical University, Shenyang, China.
Weiwei
W
Zhang
Department of Radiotherapy, The First Affiliated Hospital of China Medical University, Shenyang, China.
Huifang
H
Xia
Department of Pathology, The First Affiliated Hospital and College of Basic Medical Sciences of China Medical University, Shenyang, China. cmumiaoyuan@163.com.
Yuan
Y
Miao
Department of Pathology, The First Affiliated Hospital and College of Basic Medical Sciences of China Medical University, Shenyang, China.
Haijing
H
Zhou
Department of Pathology, The First Affiliated Hospital and College of Basic Medical Sciences of China Medical University, Shenyang, China.
Xiupeng
X
Zhang
Department of Pathology, The First Affiliated Hospital and College of Basic Medical Sciences of China Medical University, Shenyang, China.
Qianze
Q
Dong
Department of Pathology, The First Affiliated Hospital and College of Basic Medical Sciences of China Medical University, Shenyang, China.
Qingchang
Q
Li
Department of Pathology, The First Affiliated Hospital and College of Basic Medical Sciences of China Medical University, Shenyang, China.
Xueshan
X
Qiu
Department of Pathology, The First Affiliated Hospital and College of Basic Medical Sciences of China Medical University, Shenyang, China.
Enhua
E
Wang
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D015703:Antigens, CD; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010766:Phosphorylation; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D048868:Adaptor Proteins, Signal Transducing; D015703:Antigens, CD; D014408:Biomarkers, Tumor; C533047:CASS4 protein, human; C513384:CDH1 protein, human; D015820:Cadherins; D051057:Proto-Oncogene Proteins c-akt
AKT; CASS4; E-cadherin; Invasion; Non-small cell lung cancer
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