PGC-1α and ERRα in patients with endometrial cancer: a translational study for predicting myometrial invasion

Abstract

Background: PGC-1α and ERRα are closely related to tumor formation and progression. However, the mechanism underlying the involvement of PGC-1α/ERRα in regulating invasion and migration in endometrial cancer remains to be explored. Results: Elevated levels of PGC-1α and ERRα were associated with advanced myometrial invasion, and PGC-1α and Vimentin expression was related to the depth of myometrial invasion in premenopausal endometrial cancer. Silencing of PGC-1α reduced ERRα activation and inhibited epithelial-mesenchymal-transition phenotypes, resulting in significant inhibition of invasion and migration. Overexpression of ERRα led to enhanced PGC-1α expression and increased activity of TFEB, promoting epithelial-mesenchymal-transition in endometrial cancer cells. Conclusions: PGC-1α and ERRα induce the epithelial-mesenchymal-transition therefore invasion and migration in endometrial cancer, and may be novel biomarkers to predict the risk of advanced myometrial invasion. Methods: PGC-1α, ERRα, and vimentin expression was analyzed in tissue microarrays using immunohistochemistry. PGC-1α and ERRα expression in endometrial cancer cell lines was investigated using quantitative PCR and western blotting analyses after infection with lentivirus-mediated small interfering RNA (siRNA) targeting PGC-1α (siRNA-PGC-1α) or overexpressing ERRα. E-cadherin and vimentin levels were determined using western blotting and cell immunouorescence analyses. Cell migration and invasiveness were evaluated using scratch and trans-well chamber assays.

Immunohistochemical Analysis of PGC-1α and ERRα Expression Reveals Their Clinical Significance in Human Ovarian Cancer

“…Our recent research also demonstrated that inhibition of ERRα reduces EMT phenotypes, thereby significantly inhibiting invasion and migration in endometrial cancer cells. 14 ERRα expression has also been associated with negative outcome in various human cancers. For example, in breast cancer, the mRNA and protein expression of ERRα positively correlates with node status, increased risk of recurrence, and metastatic status.…”

“…In addition, we identified a novel role for PGC-1α and ERRα as positive regulators of EMT, and showed that disruption of PGC-1α/ERRα signaling could reverse EMT and inhibit endometrial cancer invasion and migration. 14 …”

“…10,13 Our recent study indicated that PGC-1α and ERRα positively correlate with more advanced myometrial invasion in endometrial cancer, and were robust predictors for myometrial invasion. 14 Currently, the suitability of PGC-1α and ERRα as biomarkers in OC tissues has not been thoroughly examined. To investigate whether the PGC-1α/ERRα axis acts as an effective prognostic marker for patients with OC, we detected the expression of these proteins in human OC tissues using immunohistochemistry and investigated their clinical significance in OC.…”

“… 10 , 13 Our recent study indicated that PGC-1α and ERRα positively correlate with more advanced myometrial invasion in endometrial cancer, and were robust predictors for myometrial invasion. 14 …”

“…and showed that disruption of PGC-1α/ERRα signaling could reverse EMT and inhibit endometrial cancer invasion and migration. 14 Currently, there are no reports in the literature on the analysis of PGC-1α and ERRα expression in OC tissues by IHC. To verify the clinical significance of PGC-1α/ERRα expression in OC, we first performed analyzed the mRNA levels of PGC-1α and ERRα in OC tissues using data from the public database HPA.…”