Cortactin expression confers a more malignant phenotype to gastric cancer SGC-7901 cells.
OBJECTIVE
To study the effects of cortactin on the tumor biology of SGC-7901 cells and identify the mechanism involved in the process.


METHODS
Cell lines in which cortactin was stably overexpressed or knocked down as well as the respective control cell lines were established by standard molecular methods. The effects of cortactin on the proliferation, migration and invasion capacity of SGC-7901 cells were assessed by the MTT assay, colony formation, flow cytometry, transwell migration and matrigel invasion. Nude mouse models were also used to assess the role of cortactin in the growth and metastasis of SGC-7901 cells in vivo. Western blotting analysis was performed to detect the expression of epidermal growth factor receptor (EGFR) and downstream molecules.


RESULTS
Cell lines in which cortactin was stably overexpressed or knocked down as well as control cell lines were successfully established and designated as LV5-cortactin-SGC, LV5-SGC, LV3-shRNA-SGC and LV3-SGC. Cortactin overexpression promoted SGC-7901 cell migration (340.7 ±12.6 vs 229.1 ± 23.2, P < 0.01) and invasion (71.6 ± 5.2 vs 48.4 ± 3.6, P < 0.01). Cortactin downregulation impaired SGC-7901 cell migration (136.2 ± 19.8 vs 225 ± 17) and invasion (29.2 ± 5.2 vs 49.6 ± 3.8, P < 0.01). The results from the MTT and colony formation assays results indicated increased LV5-cortactin-SGC cell proliferation and decreased LV3-shRNA-SGC cell proliferation compared to the control cells. Flow cytometry analysis demonstrated that cortactin overexpression promoted the proliferation index of SGC-7901 cells, and the results were reversed when cortactin was downregulated. Mouse tumor models confirmed that cortactin expression increased SGC-7901 cell proliferation and metastasis in vivo. Western blotting analysis revealed that cortactin elevated EGFR expression and activated the downstream molecules.


CONCLUSIONS
Cortactin expression promoted the migration, invasion and proliferation of SGC-7901 cells both in vivo and in vitro. The EGFR signaling pathway is mechanistically involved.
Jun Wei, Zhong-Xin Zhao, Yang Li, Zhu-Qing Zhou, Tian-Geng You, Department of Gastroenterological Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
Jun
J
Wei
Jun Wei, Zhong-Xin Zhao, Yang Li, Zhu-Qing Zhou, Tian-Geng You, Department of Gastroenterological Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
Zhong-Xin
ZX
Zhao
Jun Wei, Zhong-Xin Zhao, Yang Li, Zhu-Qing Zhou, Tian-Geng You, Department of Gastroenterological Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
Yang
Y
Li
Jun Wei, Zhong-Xin Zhao, Yang Li, Zhu-Qing Zhou, Tian-Geng You, Department of Gastroenterological Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
Zhu-Qing
ZQ
Zhou
Jun Wei, Zhong-Xin Zhao, Yang Li, Zhu-Qing Zhou, Tian-Geng You, Department of Gastroenterological Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
Tian-Geng
TG
You
D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D051356:Cortactin / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D010641:Phenotype; D013274:Stomach Neoplasms / Q000378:metabolism*
C495868:CTTN protein, human; D051356:Cortactin; C495869:Cttn protein, mouse; D066246:ErbB Receptors
Cortactin; Epidermal growth factor receptor; Gastric cancer; Invasion; Metastasis; Proliferation