Role of c-Src activity in the regulation of gastric cancer cell migration.
Gastric cancer is associated with increased migration and invasion. In the present study, we explored the role of c-Src in gastric cancer cell migration and invasion. BGC-823 gastric cancer cells were used to investigate migration following treatment of these cells with the c-Src inhibitors, PP2 and SU6656. Migration and invasion were analyzed by wound healing and Transwell assays. Western blot analysis was used to detect the expression of MT1-MMP and VEGF-C, while the activity of MMP2 and MMP9 was monitored with gelatin zymography assay. Immunoprecipitation was used to detect interactions among furin, pro-MT1-MMP and pro-VEGF-C. MT1-MMP and VEGF-C expression levels were inhibited by PP2 and SU6656 treatment, in accordance with decreased c-Src activity. Similarly, the zymography assay demonstrated that the activity of MMP2 and MMP9 was decreased following PP2 or SU6656 treatment. Blockade of c-Src also inhibited the invasive and migratory capacity of BGC-823 cells. Notably, c-Src interacted with furin in vivo, while interactions between furin and its substrates, pro-MT1-MMP and pro-VEGF-C, were decreased by c-Src inhibitors. In conclusion, the interaction among furin and pro-MT1-MMP or pro-VEGF-C or other tumor-associated precursor enzymes can be regulated by c-Src activity, thus reducing or changing the expression of these enzymes in order to reduce the development of gastric cancer, invasion and metastasis.
Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Xuanwu, Beijing 100050, P.R. China.
Yun
Y
Yang
Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Xuanwu, Beijing 100050, P.R. China.
Zhi-Gang
ZG
Bai
Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Xuanwu, Beijing 100050, P.R. China.
Jie
J
Yin
Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Xuanwu, Beijing 100050, P.R. China.
Guo-Cong
GC
Wu
Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Xuanwu, Beijing 100050, P.R. China.
Zhong-Tao
ZT
Zhang
D000081247:CSK Tyrosine-Protein Kinase; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D045683:Furin / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000473:pathology*; D011743:Pyrimidines / Q000494:pharmacology*; D013274:Stomach Neoplasms / Q000473:pathology*; D013449:Sulfonamides / Q000494:pharmacology*; D042582:Vascular Endothelial Growth Factor C / Q000378:metabolism; D019061:src-Family Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
C412373:AG 1879; D007211:Indoles; D011743:Pyrimidines; C416927:SU 6656; D013449:Sulfonamides; D042582:Vascular Endothelial Growth Factor C; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; C000631346:CSK protein, human; C468731:FURIN protein, human; D045683:Furin; D053511:Matrix Metalloproteinase 14