Hence, tumor cells have to cut down the activity of AMPK to preserve their high proliferative capacity in oncogenesis. Loss of LKB1 is often a well known mechanism in suppressing AMPK activity and is normally identified in lung cancer, melanoma, gastrointestinal carcinoma and dysplastic hamartoma in Peutz Jeghers syndrome. Nevertheless, most human cancers with an intact LKB1 function nevertheless maintain low AMPK activity when exerting their tumorigenic properties, indicating that various mechanisms exist that depress AMPK activity in such cancer cells. AMPK is usually a heterotrimeric complex consisting of a catalytic alpha subunit and regulatory beta and gamma subunits. We previously reported that the AMPK subunits are differentially expressed and that different subunits have various clinical implications in the development of ovarian cancer.
Of these subunits, we located that the mRNA level of AMPK B1 was dominantly expressed and tightly correlated with AMPK activity when compared with AMPK B2 for the duration of the progression of ovarian cancer and mTOR phosphorylation other human cancers. Constant with our earlier findings, the IHC information in this study further demonstrates that AMPK B1 expression shows a stepwise reduction from early to late stage ovarian cancer. Moreover, decreased AMPK B1 expression shows a considerable association with late stage, high grade and metastatic ovarian cancers, suggesting that reduced AMPK B1 expression decreases AMPK activity and enhances the aggressiveness of sophisticated ovarian cancer.
Despite the fact that the underlying molecular mechanisms leading towards the downregulation of AMPK B1 for the duration of ovarian cancer progression stay the full report unknown, the current discovering on the underexpression of AMPK two in liver cancer cells indicates that DNA methylation and histone deacetylation could be involved in silencing the expressions of AMPK subunits in ovarian cancer cells. Our final results indicate that the inhibitory effect of AMPK B1 on cell growth is mediated via a rise in AMPK activation and a simultaneous decrease in AKT pathway activity. Within the AMPK heterotrimeric complex, the AMPK B subunit acts as a scaffold to assistance the binding in the catalytic and regulatory subunits. We postulated that AMPK B1 upregulation probably leads to an increase inside the number of AMPK heterotrimeric complexes, which, in turn, facilitates induced activation of AMPK by either microenvironemental stresses or pharmaceutical activators. In contrast, reduce AMPK B1 expression may well minimize the number of AMPK heterotrimeric complexes, which results in reduced AMPK activity in advanced ovarian cancers. A earlier study has demonstrated that knockouts of AMPK B1 and B2 led to reduced AMPK activity in most tissues and significant reductions in bone mass in mice.