Reduced Expression of Hugl 1 Contributes to the Progression of Lung Squamous Cell Carcinoma.

ABSTRACT

Cell polarity and cell-cell adhesion play a critical role in the regulation of normal tissue architecture and function. Disruption of cell adhesion and cell polarity is often associated with neoplastic tumors. Loss of apical-basal polarity in epithelial cells is one of the hallmarks of aggressive and invasive cancers. Several polarity proteins including atypical protein kinase C (aPKC), Par 6, Par 3, and Lethal giant larvae (Lgl, the human homologues of which are called Hugl 1 and Hugl 2) are localized at the leading edge of migrating cells, and play critical roles during directional migration. Herein, we investigated the expression of aPKC, Par 6, Par 3, Hugl 1, and Hugl 2 in lung squamous cell carcinoma (SqCC). An inverse correlation was observed between the expression of Hugl 1 and lung SqCC progression. Results of immunohistochemistry and real-time RT-PCR analyses showed that reduced expression of Hugl 1 predicts poor survival in lung SqCC patients. The expression of Hugl 1 was inversely correlated with both overall survival rate and tumor stage. On the other hand, no associations were observed between the expressions of Hugl 2, Par 6, and Par 3 and lung SqCC progression. These findings indicate that the reduced expression of Hugl 1 could be considered as a poor prognostic factor in human lung cancers.