P4HA3 induce la metastasi linfatica del cancro cervicale facilitando la resistenza alla ferroptosi mediata da ACLY.

The lymph node is the most common site of distant metastasis of cervical cancer (CCa), which elicits dismal prognosis and limited efficiency for treatment. Identification of the factors contributing to CCa lymphatic metastasis is needed to develop effective prevention and treatment strategies. Here, we found upregulation of prolyl 4-hydroxylase subunit alpha 3 (P4HA3), an α-subunit of prolyl hydroxylase, in lymphatic metastatic lesions of cervical cancer, which is strongly associated with poor prognosis. In vitro and in vivo experiments showed that P4HA3 promoted CCa lymphatic metastasis by conferring ATP-citrate lyase (ACLY)-mediated ferroptosis resistance. Mechanistically, P4HA3 stabilizes