<p>Overexpressed PKMYT1 promotes tumor progression and associates with poor survival in esophageal squamous cell carcinoma</p>

Abstract

BackgroundEsophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors worldwide and the 5-year overall survival rate remains poor. Protein kinase, membrane associated tyrosine/threonine (PKMYT1) is overexpressed in several cancers and participate in tumor progression. However, the mechanism of PKMYT1 in ESCC is unclear.PurposeThe objective of our study was to demonstrate the the expression and role of PKMYT1 in ESCC.Patients and methods We detected the expression of PKMYT1 in ESCC patients and analysed the correlation with overall survival time and disease-free survival time. Then we detected PKMYT1 expression in ESCC cell lines and immortalized human esophageal epithelial cell line. Down-regulated PKMYT1 was carried out in KYSE70 and KYSE450 cells to invetigate the mechanism of PKMYT1 in ESCC cells.ResultsPKMYT1 was up-regulated in tumor tissues and ESCC cell lines, and higher expression of PKMYT1 correlated with poorer overall survival in ESCC patients. Besides, in ESCC cell lines KYSE70 and KYSE450, knocking down PKMYT1 allowed more cells to skip G2/M checkpoint to complete mitosis, which promoted cell apoptosis, inhibited cell proliferation, and prevented the EMT phenotype in vitro. Meantime, we also observed that down-regulated PKMYT1 in ESCC cells suppressed AKT/mTOR signaling pathway. These results demonstrated PKMYT1 may act as an oncogene in ESCC.ConclusionPKMYT1 plays an crutial role in ESCC progression, downregulated PKMYT1 might inhibit the development of ESCC by AKT/mTOR signaling pathway, and might be a novel target in the treatment of ESCC.

Overexpression of PKMYT1 Facilitates Tumor Development and Is Correlated with Poor Prognosis in Clear Cell Renal Cell Carcinoma

“…Consistent with the present results, PKMYT1 has been shown to be upregulated in oncogenesis and progression of multiple human tumors, including colorectal cancer [ 49 ], esophageal squamous cell carcinoma (ESCC) [ 11 ], hepatocellular carcinoma (HCC) [ 22 ], non-small-cell lung cancer (NSCLC) [ 24 ], gastric cancer (GC) [ 21 ], and breast cancer [ 13 ], as well as OC [ 23 ]. These reports have also revealed a significant correlation between increased PKMYT1 expression and advanced clinical stage and progressive histological grade, as well as unsatisfactory prognosis of diversiform tumors [ 11 , 13 , 21 – 24 , 49 ], which coincides with the results from our study. One report revealed that mutation in the C-terminal domain of PKMYT1 influenced the prognosis of neuroblastoma by altering its catalytic activity [ 50 ].…”

“…Another report revealed that depletion of PKMYT1 suppressed the β-catenin/TCF pathway, which is considered a driver of the EMT in multiple tumors and that the gene can interact with primary EMT-related biomarkers, such as Twist, Snail, and Slug [ 22 , 52 , 53 ]. Similarly, downregulation of PKMYT1 impeded Twist expression by hindering the Akt/mTOR pathway, thus suppressing migration and metastasis as well the EMT process in ESCC cells [ 11 ]. Considering that EMT is a crucial determinant for tumor metastasis and progression [ 52 , 53 ], targeting the β-catenin/TCF and Akt/mTOR pathway through PKMYT1 may be a promising strategy for tumor treatment.…”

<p>PKMYT1 Promotes Gastric Cancer Cell Proliferation and Apoptosis Resistance</p>

“…22 Other studies have detected differential expression of PKMYT1 in lung, esophageal, and colorectal cancers. [23][24][25] In this study, we first confirmed that PKMYT1 was upregulated in GC tissues and that high expression of PKMYT1 was an independent risk factor for poor prognosis in patients with GC. In terms of cell function, we found that the knockdown of PKMYT1 affected the GC cell cycle, inhibited the proliferation ability GC cells, and promoted GC cell apoptosis.…”

A WEE1 family business: regulation of mitosis, cancer progression, and therapeutic target

“…In neuroblastic tumors, PKMYT1 is required to stabilize MYCN protein, which is a crucial proto-oncogene for this cancer types [ 52 ]. Moreover, in esophageal squamous cell carcinoma (ESCC) cell lines and primary cells, the expression of PKMYT1 is associated with and regulates the activation of the AKY/mTOR pathway [ 53 ] (Table 1 ). Taken together, this evidence suggests a broad role of WEE1/PKMYT1 besides the DNA damage response pathway that may increase the interest towards its therapeutic targeting.…”