Inhibin βA is an independent prognostic factor that promotes invasion via Hippo signaling in non-small cell lung cancer

Inhibin beta A (INHBA) serves a prognostic and tumor-promoting role in numerous types of cancer. The present study aimed to determine the clinical significance of INHBA in non-small cell lung cancer (NSCLC) and the mechanisms underlying its potential tumor-promoting effect. INHBA expression was detected in clinical NSCLC samples using immunohistochemistry. In vivo loss- and gain-of-function studies were performed to determine the effects of INHBA on NSCLC invasion. In addition, protein and mRNA expression levels of INHBA, yes-associated protein (YAP), large tumor suppressor 1/2 kinase (LATS1/2), connective tissue growth factor, cysteine rich angiogenic inducer 61 and Merlin were assessed using western blotting and reverse transcription-quantitative PCR, respectively, to investigate the mechanism by which INHBA may affect the invasion of NSCLC. The present study revealed that INHBA was significantly upregulated in 238 clinical NSCLC samples compared with its expression levels in paired adjacent non-cancerous tissues, and in metastatic nodules compared with in primary tumors. Notably, high INHBA expression was statistically associated with clinicopathological features, including poor differentiation and advanced tumor stage. INHBA positivity was statistically related to decreased 5-year overall survival, for which INHBA was an independent prognostic factor. Furthermore, INHBA promoted NSCLC invasion in vitro. In NSCLC, INHBA expression was associated with the nuclear levels of YAP and INHBA overexpression enhanced the invasive abilities of NSCLC cells via inhibiting the Hippo pathway. Mechanistically, INHBA inhibited l LATS1/2 phosphorylation and induced YAP nuclear translocation by downregulating the protein expression levels of Merlin. In conclusion, INHBA may negatively regulate the Hippo pathway to act as a tumor promotor, and could represent a marker of prognosis in NSCLC.

Automated summary

The study revealed that high expression of INHBA in clinical NSCLC is associated with advanced tumor stage and poor prognosis, and it can enhance the invasive abilities of NSCLC by modulating the Hippo pathway.