Overexpression of 14-3-3 ζ primes disease recurrence, metastasis and resistance to chemotherapy by inducing epithelial-mesenchymal transition in NSCLC

In this study, we found that overexpression of 14-3-3ζ was more frequent in NSCLC tumor tissues with tumor recurrence. By using scratch healing assay and transwell assay, we demonstrated that NSCLC cells with high expression of 14-3-3ζ gained increased motile and invasive capacity, whereas siRNA-mediated knockdown of endogenous 14-3-3ζ abrogated cancer cell dissemination. Intriguingly, we found that NSCLC cells underwent epithelial-mesenchymal transition (EMT) after the induction of 14-3-3ζ in vitro and in vivo. These findings could be readily recaptured in clinical setting since we showed that NSCLC tumor specimen with high expression of 14-3-3ζ revealed biological features of EMT. Overexpression of 14-3-3ζ also enhanced the phosphorylation of Akt and promoted the proliferation of NSCLC cell lines. In agreement with this notion, we reported that NSCLC cells with high expression of 14-3-3ζ became resistant to chemotherapy-induced apoptosis. These findings strongly suggested that 14-3-3ζ as a novel biomarker predicting risks of disease recurrence and screening 14-3-3ζ status may be a promising approach to select patients who experienced high risks of cancer recurrence and resistance to chemotherapy.PMID:35876652 | DOI:10.18632/aging.204188
Source: Aging - Category: Biomedical Science Authors: Source Type: research