| Esophageal cancer is one of the common malignant tumors. Squamous cell carcinoma is the most prevalent type in China. Metastasis is the major cause of death in patients with esophageal cancer. Anoikis resistance is important for tumor cells metastasis.Oncoprotein CTTN could protect esophageal cancer cells from anoikis via activation of AKT signaling pathway. Our previous work showed KIAA1522and IQGAP1could interact with the PRD and SH3domain of CTTN in esophageal cancer cells using GST-pulldown technology. KIAA1522is a novel uncharacterized protein. KIAA1522has a proline-rich FH1domain which could associate with a number of adhesion and actin binding proteins. Gene Expression Atlas and EMBL-EBI showed up-regulation of KIAA1522mRNA in a variety of tumor tissues, suggesting that KIAA1522plays a role in the development and progression of human cancer.The immunohistochemistry results showed that the expression of KIAA1522protein in61.75%of esophageal carcinomas but only1.58%of adjacent normal tissues. By Realtime-PCR analysis we found that KIAA1522transcriptl mainly expressed in tumorous and normal tissues of the esophagus. Western blot showed that the molecular weight of KIAA1522protein was170KD. Functional studies indicated that KIAA1522could activate the S6K signaling pathway and promote the proliferation and growth of esophageal tumor cells via enhancing the transcription regulation of IQGAP1. KIAA1522could positively regulate the expression of Cadherin/Catenin complexes β-catenin, a-catenin, y-catenin, p120ctn, actin polymeration proteins IQGAP1, Arp3, N-WASp, VASP, CTTN, actin rearrangement proteins Paxillin and Fasin, adhesion-related kinases FAK, Src and ERK in cell-cell adhesion, which in turn resists cell anoikis. IQGAP1play a partial role in KIAA1522mediated adhersion and anoikis resistence process. By immunofluorescence and co-immunoprecipitation experiments, we could detect a colocalization of KIAA1522protein with adhesion proteins IQGAP1, CTTN,β-catenin at cell adheren junctions. CTTN and IQGAP1also could positively regulate the expression of KIAA1522protein in esophageal tumor cells. All these results indicate that KIAA1522may promote cytoskeleton polymerization and adhesion junction formation by binding and cross-regulation with IQGAP1, CTTN, thereby resist cell anoikis.IQGAP1was differently expressed in colorectal carcinoma tissues and their normal adjacent tissues, and its upregulation was associated with lymph node metastasis and clinical stage of tumors. Functional studies showed that IQGAP1also affect anoikis through regulating the expression of adheren junction proteins E-cadherin, β-catenin, a-catenin and the activation of ERK/MAPK, S6K/S6signal pathway in colorectal tumor cells. IQGAP1positively regulate the activation of ERK to protect the cells from anoikis which might be a common mechanism in colorectal cancer, esophageal cancer, lung cancer cells.In conclusion, KIAA1522and its mutual regulatory protein IQGAP1play important roles in promoting cell proliferation and anoikis resistance in esophageal cancer cells. In adherent cells, KIAA1522promote the proliferation of esophageal cancer cells by positively regulating the expression of IQGAP1of the transcriptional levels and activating the S6K signaling pathway..Upon suspension, KIAA1522fostered actin cytoskeleton polymerization and cell-cell adhesion, and protect esophageal cancer cells from anoikis. KIAA1522might promote the tumorigenesis and progression of esophageal carcinoma by positively regulating cell proliferation and cell adheren-related resistance to anokis, suggestting KIAA1522is a novel cell adhesion-mediated oncoprotein.IQGAP1could also promote cell-cell adhesion formation, and by activiting ERK and S6K signaling pathway activation, inhibite cell anoikis in suspended colorectal cancer cells. High IQGAP1expression is positively correlated with lymph node metastasis in colorectal tumor tissues, which indicating that IQGAP1functions as oncoprotein in the metastasis process of colorectal tumors. |
PDF Full Text Request