Correlations Between Transcription Factor NFAT-Integrin α₆β₄ Signal Transduction Pathway And The Invasion, Metastasis In Colorectal Carcinoma

To investigate the correlations between expressions of NFAT, integrin α₆β₄ and invasion, metastasis in colorectal carcinoma (CRC), research the mechanism of interaction between NFAT and integrin α₆β₄ in CRC development, the mRNA and protein expression levels of NFAT and integrin subunits α₆,β₄ in colorectal carcinoma and in distal normal tissues which were collected from the 30 patients with CRC were assayed by real-time Quantitative PCR and immunohistochemical S-P methods individually. All investigatory data were statistically analyzed and compared with clinico-pathological findings. The results show that:1. Both the mRNA and protein expression levels in CRC are significantly higher than that in normal control.2. In CRC, significantly positive correlations between NFAT expression and lymph node metastasis, neoplasia invasion or Dukes' stage are respectively found. However the mRNA transcription level of NFAT is correlated with primary tumor invasion only.3. There is no correlation between NFAT expression levels and histological type or pathological grade of CRC.4. Integrin subunits α₆ and β₄ mRNA and protein expressions in CRC are significantly higher than that in distal normal tissue.Conclusions:1. Overexpressions of NFAT in CRC suggest that NFAT might promoteneoplasm angiopoiesis, then lead to tumor development, invasion andmetastasis by regulating VEGF through the COX2NEGF signal transductionpathway.2. NFAT is considered as the central molecule in integrin-mediated signaltransduction pathway, which is closely relative to the acquirement of potential ability to invasion or metastasis of CRC. Therefore, NFAT could be a prognostic predictor in the evaluation of CRC patients.3. The overexpressions of integrin subunits qq and (34 suggest that thepromotion effets of NFAT to angiopoiesis, tumor invasion and metastasis could complete by NFAT itself adhesion effect and NFAT might be an active factor in the integrin-mediated IP3-Ca2+-NFAT signal transduction pathway.