Relationship between polycomb‐group protein BMI‐1 and phosphatases regulating AKT phosphorylation level in endometrial cancer

Abstract

The PI3K/AKT pathway is frequently activated in endometrial carcinoma. BMI-1 (Blymphoma Mo-MLV insertion region 1) protein affects expression of PTEN (phosphatase and tensin homolog) in some cancers, but its significance for endometrial tumorigenesis is not known. The objective of this study was to determine the relationship between BMI-1 and expression of factors affecting AKT (protein kinase B) phosphorylation level in endometrial cancer. The expression of proteins and mRNAs was investigated in endometrial cancer specimens and samples of non-neoplastic endometrial tissue by Western blot and RT-PCR, respectively. The impact of BMI-1 down-regulation on AKT phosphorylation and expression of genes coding for several phosphatases were studied in HEC1A cells. The results showed that BMI-1 depletion caused increase in PHLPP1 and PHLPP2 (PH domain and leucine-rich repeat protein phosphatases 1/2) expression and decrease in phospho-AKT (pAKT) level. In more advanced tumours with higher metastatic potential, the expression of BMI-1 was lower compared to tumours less advanced and without lymph node metastasis.There were significant inverse correlations between BMI-1 and PHLPPs, especially PHLPP1 in normal endometrial samples. The inverse correlation between BMI-1 and PHLPP1/PHLPP2 expression was observed in PTEN positive but not PTEN negative cancers. Low PHLPP2 expression in tumours predicted poorer overall survival. BMI-1 impacts on AKT phosphorylation level in endometrial cells by regulation of PHLPP expression. K E Y W O R D SAKT, BMI-1, endometrial cancer, PHLPP, PTEN | 1301 ZACZEK Et Al.

Knockdown of YKL‐40 inhibits angiogenesis through regulation of VEGF/VEGFR2 and ERK1/2 signaling in endometrial cancer

“…This study used the cell line of HEC‐1A cells (Yoshioka et al, 2013; Zaczek et al, 2020) which were purchased from the Chinese Academy of Sciences (Shanghai, China). HUVECs were obtained from ScienCell Laboratories of the United States (San Diego, USA).…”

BMI1 in the heart: Novel functions beyond tumorigenesis

“…It has also been shown that BMI1 was capable of inducing the invasion/metastasis of pancreatic cancer stem cells by activating PI3K/Akt pathway, which was negatively regulated by the tumor suppressor PTEN [45] . BMI1 and Akt were also involved in endometrial cancer, interestingly, BMI1 was downregulated and the low expression of BMI1 was intimately associated with the endometrial cancer progression, so as Akt [46] . In addition, it seemed that BMI1 influenced the level of Akt phosphorylation in endometrial cells by modulating PH domain and leucine‐rich repeat protein phosphatase (PHLPP) expression [46] .…”

“…BMI1 and Akt were also involved in endometrial cancer, interestingly, BMI1 was downregulated and the low expression of BMI1 was intimately associated with the endometrial cancer progression, so as Akt [46] . In addition, it seemed that BMI1 influenced the level of Akt phosphorylation in endometrial cells by modulating PH domain and leucine‐rich repeat protein phosphatase (PHLPP) expression [46] . These cancer models exemplifies the potential dual role of BMI1 (up- and downregulated) depending on the cancer contexts.…”

“… endometrial cancer cells BMI1 impacts on Akt phosphorylation level by regulating the expression of PHLPP. [46] Cardiac homeostasis Cardioprotective healthy hearts B-CPCs served as a significant contributor to all three main cardiac lineages, including cardiomyocytes, smooth muscle and endothelial cells. cardiac progenitor cells B-CPCs are enriched in stemness-related genes, and their upstream regulators are related to stemness and heart development.…”

“…As a major area of investigation in cancer research, BMI1 expression is often increased in cancer and is linked to tumor progression and invasion, except for endometrial cancer [46] . In nasopharyngeal carcinoma and pancreatic cancer, BMI1 activates the PI3K/Akt signaling pathway to promote tumor relapse [ 44 , 45 ].…”