Beta-catenin knockdown impairs the viability of ovarian cancer cells by modulating YAP-dependent glycolysis.

OBJECTIVES

Ovarian cancer (OC) ranks fifth among the main causes of cancer-related deaths in women worldwide. PCLAF/KIAA0101 and Yes-associated protein (YAP) have been linked to several human malignant cancers, including OC. However, the roles of KIAA0101 and YAP in glycolysis-dependent OC cell proliferation remain unknown.

METHODS

qRT-PCR and western blot were performed to analyze the KIAA0101 expression. Short hairpin RNA transfection was performed to silence KIAA0101 expression in cells. Cell viability and apoptosis were assayed by colony formation and flow cytometry, respectively. Glucose uptake, lactate production, and glycolytic enzyme expression were assessed to determine the level of cellular glycolysis. Phosphorylation and the nuclear localization of YAP were assessed to determine YAP activation.

RESULTS

OC tissue and cell lines exhibited higher KIAA0101 expression than the non-cancerous tissues and cells. KIAA0101 silencing reduced the proliferation and increased the apoptosis of both A2780 and ES-2 OC cell lines. Furthermore, KIAA0101 depletion suppressed glycolysis and YAP activation, as evidenced by increased YAP phosphorylation and decreased nuclear localization. Reactivation of YAP was performed by administration of mitochonic acid 5 in both OC cell lines with KIAA0101 knockdown. Glucose uptake, lactate production, phosphofructokinase, pyruvate dehydrogenase beta, pyruvate kinase M2, triosephosphate isomerase 1, glucose-6-phosphate dehydrogenase, enolase 1, and lactate dehydrogenase expression levels in cells recovered after the reactivation of YAP. Additionally, YAP reactivation increased cell proliferation and inhibited apoptosis.

CONCLUSIONS

This study showed that KIAA0101 could promote glycolysis during nasopharyngeal carcinoma development through YAP signaling activation, suggesting that KIAA0101 could serve as a target for OC treatment.