Abstract
Abstract The transcription factor PITX2 (paired-like homeodomain 2) is well known to play an essential role in normal embryonic development. Emerging evidence suggests that PITX2 may be involved in human tumorigenesis. However, the functional role that PITX2 plays in tumor progression remain unclear. In this study, we investigated its function in human non-small cell lung carcinoma (NSCLC). Using real-time quantitative RT-PCR, we demonstrated that PITX2B is the most abundant isoform in lung cancer cells. Enforced expression of PITX2B could promote lung cancer cell morphological change, migration, invasion, anchorage-dependent growth ability and tumorigenesis in xenograft model mice. In addition, nuclear PITX2B localization was correlated with its oncogenic functions and two important nuclear localization signals (NLSs) were identified. Moreover, high expression of PITX2B was associated with poor overall survival (P<0.05) in NSCLC patients. Importantly, silencing of PITX2B by siRNA caused a marked increase in autophagy based on LC3-II, Beclin-1, and p62 protein expression, acridine orange fluorescence of acidic vacuoles and electron microscopic detection of autophagosomes. Furthermore, we found that the autophagy induced by PITX2B knockdown preceded apoptosis in lung cancer cells. Treatment of lysosome inhibitor, NH4Cl, could provide a protective effect that increases cell viability. In conclusion, our studies not only provide new insights into how PITX2B may contribute to the tumor progression in lung cancer but also the autophagy induced by PITX2B knockdown that may be developed as an effective therapeutic strategy for the treatment of lung cancer. Citation Format: Sheng-Yi Lin, Yu-Han Huang, Yi-Hua Lai, Sung-Liang Yu, Sheng-Fang Su, Tse-Ming Hong, Gee-Chen Chang, Chi-Chung Wang, Jeremy J.W. Chen. The role of paired-like homeodomain 2B in non-small cell lung cancer progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4450. doi:10.1158/1538-7445.AM2017-4450
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