Overexpression of PKMYT1 indicates the poor prognosis and enhances proliferation and tumorigenesis in non-small cell lung cancer via activation of Notch signal pathway.

OBJECTIVE:The protein kinase, membrane‑associated tyrosine/threonine 1 (PKMYT1) has been implicated as an important factor promoting the tumorigenesis of hepatocellular carcinoma and colorectal cancer. The current study was designed to explore the functional role of PKMYT1 in non-small cell lung cancer (NSCLC) cell behaviors and to investigate the possible molecular mechanisms. PATIENTS AND METHODS:The expression levels of PKMYT1 in NSCLC tissues and cell lines were determined by quantitative Real (qRT-PCR). The clinical and prognostic significance of PKMYT1 in 153 cases of NSCLC was determined. We also evaluated the effects of KMYT1 on NSCLC cell proliferation, migration, and invasion in vitro. Western blot was performed to assure whether PKMYT1 affected the Notch signal pathway and MET pathway. RESULTS:We observed that PKMYT1 expression was significantly up-regulated in both NSCLC tissues and cell lines. Higher expression of PKMYT1 was associated with clinical stage and lymph nodes metastasis. Clinical survival assays demonstrated that patients with high PKMYT1 expression had a shorter overall survival time than those with low PKMYT1 expression. Moreover, the multivariate analysis confirmed that increased expression of PKMYT1 was an independent predictor of overall survival. Functionally, knockdown of PKMYT1 in the NSCLC cell lines A549 and H1299 suppressed NSCLC cells proliferation, invasion and migration, and promoted apoptosis. In addition, the down-regulation of PKMYT1 resulted in the inhibition of EMT in NSCLC cells. Further mechanistic studies revealed that when PKMYT1 was silenced, the expression levels of Notch1, p21, and Hes1 were respectively downregulated, suggesting that PKMYT1 could promote the activity of the Notch signal pathway. CONCLUSIONS:PKMYT1 plays a significant role in NSCLC aggressiveness and clinical outcome, and may serve as a promising therapeutic target for this disease.

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