Cortactin contributes to the tumorigenicity of colorectal cancer by promoting cell proliferation.
Cortactin is a scaffolding protein that regulates Arp2/3-mediated actin polymerization. We showed in a previous study that cortactin was highly expressed in human stage II-III colorectal cancer (CRC) tissues. In the present study, using colony formation and CCK-8 assays, we showed that overexpression of cortactin accelerated the proliferation of CRC cells. Flow cytometric assays revealed that cortactin promoted G1/S phase cell cycle transition. Later, we constructed the phosphorylation mutation of cortactin at the Tyr421 residue. Colony formation and CCK-8 assays showed that cortactin/Tyr421A lost its ability to promote cell proliferation. Western blot analysis indicated that cortactin activated cyclin D1, but not cortactin/Tyr421A. Further study in nude mice revealed that there was a greater decrease in both tumor volume and tumor weight in animals injected with SW480/cortactin/Tyr421A cells than in those injected with SW480/cortactin/WT cells. Thus, the present study demonstrates that the cortactin Tyr421 residue is required to promote cell proliferation both in vitro and in vivo.
Department of General Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China.
Huo
H
Wu
Department of General Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China.
Xi
X
Cheng
Department of General Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China.
Xiaopin
X
Ji
Department of General Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China.
Yonggang
Y
He
Department of General Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China.
Xiaoqian
X
Jing
Department of General Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China.
Haoxuan
H
Wu
Department of General Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China.
Ren
R
Zhao
D000818:Animals; D063646:Carcinogenesis / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D051356:Cortactin / Q000502:physiology*; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D059585:G1 Phase Cell Cycle Checkpoints; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D020125:Mutation, Missense; D015533:Transcriptional Activation
C530104:CCND1 protein, human; C495868:CTTN protein, human; D051356:Cortactin; D019938:Cyclin D1