Aquaporins (AQP) play important roles in water and glycerol transport. We examined whether AQP3 is expressed in primary squamous cell carcinoma (SCC) such as esophageal and oral cancer and lymph node metastasis, and whether AQP3 is a potential target for tumor therapy. A high level expression of AQP3 was observed in tumor areas of human primary SCC such as esophageal and lingual cancers, and lymph node metastasis, but was not observed in normal areas. Treatment with pan-AQP inhibitor caused apoptotic cell death on the SCC cell lines in a concentration-dependent manner. Small interfering RNA (siRNA) specific for AQP3 also inhibited cell adhesion and growth of SCC, but not those of adenocarcinoma cell lines and fibroblasts. Expression of integrin a5 and b1, counter adhesion molecules for fibronectin, was inhibited by treatment with AQP3-siRNA. The phosphorylation of focal adhesion kinase (FAK) was decreased by treatment with AQP3-siRNA, which then caused decreases in phosphorylation of Erk and MAPK. These results indicate that the decreases in integrins and the inhibition of cell adhesion might cause inhibition of the FAK signaling pathways. Combination of AQP3-siRNA with cisplatin, a major anti-cancer drug, strongly inhibited the growth of SCC. Cell death caused by the inhibition of AQP3 was a result of direct interference with cell adhesion involving intracellular FAK-MAPK signaling pathways. These results imply a potentially important and novel role for the inhibition of AQP3 function via the use of specific siRNA in the treatment of SCC. (Cancer Sci 2011; 102: 1128-1136 H uman squamous cell carcinoma (SCC) is a major neoplasm in the esophagus or oral cavity and its incidence has recently been increasing.(1-3) The optimal treatment or therapy for early carcinoma is a surgical operation. However, overall survival remains largely unchanged.(1,3,4) Therefore, different therapies for the inhibition of tumor cell growth are required.The aquaporin (AQP) family is a membrane protein involved in the selective transport of water across cell membranes. Several subsets of AQP also transport small molecules such as glycerol and urea.(5-9) Among them, AQP3 is known to be expressed in various organs such as kidney, skin, lung and gastrointestinal tracts and to play important roles in the transport of water and glycerol. (10)(11)(12) Recent studies reported the expression of AQP3 in several cancers such as skin, lung and prostate. (13)(14)(15)(16)(17) However, there are few reports about the exact role of AQP3 on the cell growth of squamous cell carcinomas (SCC) such as esophageal or lingual cancers.We investigated whole genome analysis using a DNA microarray to find potential target genes that are involved in tumor cell growth, and reported the critical role of several important molecules on the cell growth of SCC. (18)(19)(20)(21) According to previous study and the results of a DNA microarray, we found that expression of AQP3 mRNA was observed in cell lines of SCC and the AQP3 expression level was altered by the inhibitio...

Abstract. Myeloid cell leukemia-1 (Mcl-1), a member of the B-cell lymphoma-2 (Bcl-2) family, has been reported to be a critical survival factor in hematopoietic cells, yet little data exists for a role of Mcl-1 in human oral squamous cell carcinoma (SCC) .