The role of polarity proteins Par6B and Par6G in cell proliferation

The majority of cancers, such as breast cancer, originate from epithelial structures. Highly organized epithelial tissues are comprised of cells which manifest apico-basal polarization. Factors regulating apico-basal polarity and epithelial integrity are often observed deregulated in cancer cells and loss of polarity is often observed in tumors. However, the importance and the specific role of epithelial integrity regulators in tumorigenesis are still not fully defined. This study shows that the key regulators of epithelial cell polarity Par6B and Par6G proteins have a role in the restriction of cell proliferation in mammary epithelial cell lines. Using the shRNA silencing approach, downregulation of PARD6B and PARD6G in the cells lead to the impediment of the cell-cycle exit, verified in proliferation suppressive conditions in which cells normally would enter quiescence. Par6 proteins were shown to regulate cell proliferation via the canonical PI3K/Akt pathway, which is one of the most commonly deregulated cell proliferation promoting pathways in cancer cells. The results demonstrate the unknown function of Par6B and Par6G proteins as cell proliferation regulators and a previously unrecognized relation between Par6 proteins and PI3K/Akt pathway. However, the detailed interaction between Par6 proteins and the PI3K/Akt pathway ought to be investigated further. In addition, the results revealed that Par6 proteins have different effects on cell proliferation suggesting biological differences between Par6 proteins and that certainly bears further investigation. In conclusion, the study presents a previously unknown connection between epithelial integrity regulators and cancer-relevant cell proliferation promoting pathways, which may provide new targets for therapeutic intervention in the future