PURPOSE: Connexin 26 (Cx26) is one of the gap junction-forming family members classically considered to be tumor suppressors. However, recent studies show association of elevated expression of Cx26 with poor prognosis in several human malignancies. Furthermore, Cx26 has been observed to be indispensable to spontaneous metastasis of melanoma cells. Here, we assessed Cx26 expression in primary colorectal cancer (CRC) and the metastatic lesions to elucidate its role in metastasis. EXPERIMENTAL DESIGN: Cx26 expression was assessed in 25 adenomas, 167 CRCs, and normal mucosa, together with the metastatic lesions. RESULTS: Normal mucosa and adenomatous tissue expressed Cx26 mainly in the plasma membrane, whereas cancer cells mostly contained Cx26 in the cytoplasm. The incidence of aberrant Cx26 expression varied widely in CRC (mean, 49.5 +/- 35.5%), and the expression levels were confirmed by Western blot and quantitative reverse transcription-PCR. Clinicopathologic survey revealed association of high expression with less differentiated histology and venous invasion (P = 0.0053 and P = 0.0084, respectively). Notably, high Cx26 expression was associated with shorter disease-free survival and shorter lung metastasis-free survival in 154 curatively resected CRC sets (P = 0.041 and P = 0.028, respectively). Survey of metastatic lesions revealed that lung metastasis, but not liver and lymph nodes metastases, expressed higher Cx26 than the CRC series or corresponding primary CRCs (P < 0.0001 and P = 0.0001, respectively). CONCLUSIONS: These findings suggest that aberrant expression of Cx26 plays an essential role in lung metastasis. Thus, Cx26 is a promising therapeutic target, particularly for CRC patients who develop lung metastasis.
PURPOSE:Connexin 26 (Cx26) is one of the gap junction-forming family members classically considered to be tumor suppressors. However, recent studies show association of elevated expression of Cx26 with poor prognosis in several humanmalignancies. Furthermore, Cx26 has been observed to be indispensable to spontaneous metastasis of melanoma cells. Here, we assessed Cx26 expression in primary colorectal cancer (CRC) and the metastatic lesions to elucidate its role in metastasis. EXPERIMENTAL DESIGN:Cx26 expression was assessed in 25 adenomas, 167 CRCs, and normal mucosa, together with the metastatic lesions. RESULTS: Normal mucosa and adenomatous tissue expressed Cx26 mainly in the plasma membrane, whereas cancer cells mostly contained Cx26 in the cytoplasm. The incidence of aberrant Cx26 expression varied widely in CRC (mean, 49.5 +/- 35.5%), and the expression levels were confirmed by Western blot and quantitative reverse transcription-PCR. Clinicopathologic survey revealed association of high expression with less differentiated histology and venous invasion (P = 0.0053 and P = 0.0084, respectively). Notably, high Cx26 expression was associated with shorter disease-free survival and shorter lung metastasis-free survival in 154 curatively resected CRC sets (P = 0.041 and P = 0.028, respectively). Survey of metastatic lesions revealed that lung metastasis, but not liver and lymph nodes metastases, expressed higher Cx26 than the CRC series or corresponding primary CRCs (P < 0.0001 and P = 0.0001, respectively). CONCLUSIONS: These findings suggest that aberrant expression of Cx26 plays an essential role in lung metastasis. Thus, Cx26 is a promising therapeutic target, particularly for CRC patients who develop lung metastasis.
Authors: Tarso Felipe Teixeira; Luciana Boffoni Gentile; Tereza Cristina da Silva; Gregory Mennecier; Lucas Martins Chaible; Bruno Cogliati; Marco Antonio Leon Roman; Marco Antonio Gioso; Maria Lucia Zaidan Dagli Journal: Vet Res Commun Date: 2013-10-15 Impact factor: 2.459
Authors: Rita Nahta; Fahd Al-Mulla; Rabeah Al-Temaimi; Amedeo Amedei; Rafaela Andrade-Vieira; Sarah N Bay; Dustin G Brown; Gloria M Calaf; Robert C Castellino; Karine A Cohen-Solal; Annamaria Colacci; Nichola Cruickshanks; Paul Dent; Riccardo Di Fiore; Stefano Forte; Gary S Goldberg; Roslida A Hamid; Harini Krishnan; Dale W Laird; Ahmed Lasfar; Paola A Marignani; Lorenzo Memeo; Chiara Mondello; Christian C Naus; Richard Ponce-Cusi; Jayadev Raju; Debasish Roy; Rabindra Roy; Elizabeth P Ryan; Hosni K Salem; A Ivana Scovassi; Neetu Singh; Monica Vaccari; Renza Vento; Jan Vondráček; Mark Wade; Jordan Woodrick; William H Bisson Journal: Carcinogenesis Date: 2015-06 Impact factor: 4.944
Authors: Srikanth R Polusani; Edward A Kalmykov; Anjana Chandrasekhar; Shoshanna N Zucker; Bruce J Nicholson Journal: J Cell Sci Date: 2016-10-24 Impact factor: 5.285
Authors: Marcelo Monte Mór Rangel; Lucas Martins Chaible; Marcia Kazumi Nagamine; Gregory Mennecier; Bruno Cogliati; Krishna Duro de Oliveira; Heidge Fukumasu; Idércio Luiz Sinhorini; Lluis Maria Mir; Maria Lúcia Zaidan Dagli Journal: J Membr Biol Date: 2014-10-09 Impact factor: 1.843