PAPSS2 inhibits proliferation and metastasis of papillary thyroid cancer cells by mediating ferroptosis and disulfidptosis through the AKT signaling pathway

Abstract

Abstract Papillary thyroid cancer (PTC) is the most common type of thyroid cancer(Derwich, Sykutera et al. 2023). Unfortunately, lymph node metastasis often occur in early stage of PTC, while the specific mechanism is still unclear(Wei, Wei et al. 2023). Previous in vivo study showed that PAPSS2 is a rate-limiting enzyme of the sulfation pathway. Interestingly, it has been known that the expression of PAPSS2 in PTC biopsy samples was significantly lower than that in paracancerous tissues. Bioinformatics analysis and preliminary study suggested that PAPSS2 might affect the metabolism of glycosaminoglycan sulfation and damage the extracellular matrix barrier by inhibiting the sulfation pathway, thus providing a suitable microenvironment for tumor metastasis. Our study showed that PAPSS2 could regulate ferroptosis and disulfidptosis of thyroid cancer cells through regulating the AKT signaling pathway and thereby induce cytoskeletal changes and lymph node metastasis. Our findings not only identified a novel therapeutic target but also shed light upon a better understanding of the pathogenesis of PTC.