The study of RunX3 in tumor pathogenesis is a rapidly expanding area of cancer research.Functional inactivation of RunX3 is frequently observed in tumors of diverse origins.RunX3 can bind directly to the TGF-β signaling effectors for synergistic induction,enhancing the growth inhibitory effect of TGF-β signal pathway.Additionally,RunX3 can also bind to the complex TCF4-β-catenin in Wnt signal pathway for inhibiting its tumorigenicity.Through the two signal pathway mentioned above,RunX3 can regulate the epithelial mesenchymal transitions process.Moreover,the transcription of claudin-1 can be directly regulated by RunX3.RunX3 has also been described to have an oncogenic function in a subset of tumors,but how RunX3 switches from tumor suppression to oncogenic activity is yet unknown.This review focuses on summarizing the important findings about the mechanism and relative signal pathway of RunX3 in tumor suppression from the articles published recently.

OBJECTIVETo investigate Runx3 and C-myc expressions in colorectal cancer and their relationship with the clinicopathological parameters.

METHODSReal-time quantitative PCR was used to detect Runx3 and C-myc mRNA expressions in 38 colorectal cancer tissues and matched adjacent tissues, and Runx3 and C-myc expressions was detected by Western blotting in 63 pairs of colorectal cancer and adjacent tissues. The results were stratified according to the clinicopathological characteristics to examine the relationship of Runx3 and C-myc expressions with the clinicopathological factors in the patients.

RESULTSRunx3 expression was down-regulated and C-myc expression up-regulated at both mRNA and protein levels in colorectal cancer tissues compared with the normal tissues, and their protein expressions exhibited an inverse correlation (r=-0.398, P=0.001). Runx3 and C-myc expressions differed significantly between tumors with different Dukes stages, depths of tumor invasion, lymph node statuses, or histological differentiation (P<0.05); Runx3 down-regulation and C-myc up-regulation were more obvious in tumors in advanced Dukes stage and in poorly differentiated tumors.

CONCLUSIONAbnormal expressions in Runx3 and C-myc may contribute to the occurrence and development of colorectal cancer and are closed correlated with the patient's clinicopathological parameters.

Blotting, Western ; Cell Differentiation ; Colorectal Neoplasms ; genetics ; metabolism ; Core Binding Factor Alpha 3 Subunit ; genetics ; metabolism ; Down-Regulation ; Humans ; Proto-Oncogene Proteins c-myc ; genetics ; metabolism ; RNA, Messenger ; Real-Time Polymerase Chain Reaction ; Up-Regulation

OBJECTIVE: To explore the association between expression of ADAM17 and cetuximad resistance in human colorectal cancer SW480 cells. METHODS: The expression of ADAM17 was detected using Western blotting in different human colorectal cancer cell lines, and the cells highly expressing ADAM17 were selected as the target cells. SW480 cells were transfected with ADAM17-siRNA 1 and ADAM17-siRNA 2 and the changes in the expression of ADAM17 protein were detected using Western blotting. SW480 cells were exposed to cetuximad for 24 h and the cell apoptosis was analyzed using flow cytometry. Transwell assay was used to examine the migration ability of SW480 cells with different expression levels of ADAM17; Western blotting was used to analyze the changes in the expressions of AKT signaling pathway-related proteins in the treated cells. RESULTS: The baseline expressions of ADAM17 were significantly higher in SW480 cells than in the other human colorectal cancer cell lines tested ( < 0.05). Both ADAM17-siRNA 1 and 2 effectively reduced the expression of ADAM17 protein in SW480 cells. Knockdown of ADAM17 with siRNA 1 significantly increased the sensitivity of SW480 cells to tocetuximad ( < 0.05), obviously inhibited the cell proliferation, migration and invasion, and significantly reduced the expressions of p-EGFR and p-AKT in the cells ( < 0.001). CONCLUSIONS ADAM17 knockdown obviously inhibits EGFR-AKT signaling pathway and increases the sensitivity of SW480 cells to tocetuximad.
ADAM17 Protein ; genetics ; metabolism ; Antineoplastic Agents, Immunological ; pharmacology ; Apoptosis ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Cetuximab ; pharmacology ; Colorectal Neoplasms ; drug therapy ; genetics ; metabolism ; pathology ; Drug Resistance, Neoplasm ; genetics ; ErbB Receptors ; metabolism ; Gene Knockdown Techniques ; Humans ; Neoplasm Invasiveness ; Oncogene Protein v-akt ; metabolism ; RNA, Small Interfering ; Signal Transduction ; Transfection ; methods