Targeted silencing of CXCR4 inhibits epithelial-mesenchymal transition in oral squamous cell carcinoma.
Aberrant overexpression of C-X-C chemokine receptor type 4 (CXCR4) is a critical event during tumor metastasis. It has been previously reported that the expression of CXCR4 is linked with epithelial-mesenchymal transition (EMT) in oral squamous cell carcinoma (OSCC) tissues derived from patients. The present study addresses the role of CXCR4 in EMT in tongue squamous cell carcinoma (TSCCA) cellsin vitroand in xenograft models. Small interfering (si) RNA sequences targeting the CXCR4 gene were transfected into TSCCA cells. Cell migration, invasion, apoptosis and EMT markers were determined in TSCCA cells using wound healing and Transwell assays, Annexin V/propdidum iodide double staining and western blot analysis, respectively.In vivo, tumor growth was assessed by subcutaneous inoculation of cells into BALB/c nude mice. Phenotypic EMT markers and regulatory factors were detected in the tumor tissues derived from the mice.In vitro, silencing of CXCR4 expression suppressed cell migration and invasion, and induced apoptosis. The protein expression of the EMT-associated markers N-cadherin and matrix metalloproteinases 2/9 were attenuated, while E-cadherin was increased.In vivo, CXCR4 siRNA inhibited tumor growth, and EMT-associated proteins had similar expression patterns to the experimental results observedin vitro. In conclusion, the present study demonstrated that CXCR4 silencing suppressed EMT in OSCC, thus affecting tumor metastasis.
Department of Maxillofacial and E.N.T Oncology, Tianjin Medical University Cancer Institute & Hospital, Tianjin 300060, P.R. China; National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, P.R. China.
Yuansheng
Y
Duan
Department of Maxillofacial and E.N.T Oncology, Tianjin Medical University Cancer Institute & Hospital, Tianjin 300060, P.R. China; National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, P.R. China.
Shu
S
Zhang
Department of Thyroid Surgery, Baotou Cancer Hospital, Baotou, Inner Mongolia 014030, P.R. China.
Longlong
L
Wang
Department of Maxillofacial and E.N.T Oncology, Tianjin Medical University Cancer Institute & Hospital, Tianjin 300060, P.R. China; National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, P.R. China.
Xuan
X
Zhou
Department of Maxillofacial and E.N.T Oncology, Tianjin Medical University Cancer Institute & Hospital, Tianjin 300060, P.R. China; National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, P.R. China.
Qinghua
Q
He
Department of Maxillofacial and E.N.T Oncology, Tianjin Medical University Cancer Institute & Hospital, Tianjin 300060, P.R. China; National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, P.R. China.
Su
S
Liu
Department of Maxillofacial and E.N.T Oncology, Tianjin Medical University Cancer Institute & Hospital, Tianjin 300060, P.R. China; National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, P.R. China.
Kai
K
Yue
Department of Maxillofacial and E.N.T Oncology, Tianjin Medical University Cancer Institute & Hospital, Tianjin 300060, P.R. China; National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, P.R. China.
Xudong
X
Wang
CXCR4; epithelial-mesenchymal transition; knockdown; metastasis; oral squamous cell carcinoma