INTRA-GOLGI CONNEXIN26 BEHAVES IN A PRO-ONCOGENIC MANNER IN HEAD AND NECK CANCER CELLS

Downregulation of gap junctional intercellular communication is an important hallmark of malignant tumours. One of the downregulation mechanisms is translocation of gap junction (GJ) protein called connexin from cell membrane into cytoplasm, nucleus, or Golgi apparatus. Interestingly, as tumours progress and reinforce their malignant phenotype, the amount of aberrantly-localised connexin increases in different cancers including oesophageal squamous cell carcinoma, thus suggesting that such an aberrantly-localised connexin should be oncogenic. To determine the roles of aberrantly-localised connexin in head and neck squamous cell carcinoma (HNSCC), we introduced wild-type connexin26 (wtCx26) or the Golgi-retained mutant Cx26 (mtCx26) gene into human SAS lingual HNSCC cell line, which had lost the expression of connexin during carcinogenesis. The wtCx26 protein was trafficked to cell membrane and formed GJ, which successfully exerted cell-cell communication. On the other hand, mtCx26 protein was retained in the Golgi apparatus on the way to cell membrane. While the forced expression of wtCx26 suppressed various malignant phenotypes including cell proliferation, motility, and invasiveness in vitro, mtCx26 significantly reinforced these phenotypes compared with the mock control clone, indicating that an excessive accumulation of connexin protein in Golgi apparatus should be involved in cancer progression.