biostudies-literatureUnknown27(7)Fei HLymph node metastasis (LNM) is the main metastatic pathway of cervical cancer, which is closely related to 5-year survival rate of cervical squamous cell carcinoma (CSCC), yet the underlying mechanism remains unconfirmed. In this study, we show that midkine (MDK) was highly expressed in CSCC and overexpression of MDK was associated with CSCC LNM. Functional investigations demonstrated that MDK promoted LNM by enhancing proliferation, migration and invasion capacity of cervical cancer cells, facilitating lymphangiogenesis and down-regulating the expression of tight junction proteins of human lymphatic endothelial cells (HLECs). MDK exerted these biological effects by interacting with Syndecan-1 and activating PI3K/AKT and p38 MAPK pathways. A retrospective study showed that s-MDK was relateiScience110077https://www.ebi.ac.uk/biostudies/studies/S-EPMC11261016biostudies-literatureAutocrine and paracrine effects of MDK promote lymph node metastasis of cervical squamous cell carcinoma.PMC11261016Jiang HFei HChen TfalseAutocrine and paracrine effects of MDK promote lymph node metastasis of cervical squamous cell carcinoma.Lymph node metastasis (LNM) is the main metastatic pathway of cervical cancer, which is closely related to 5-year survival rate of cervical squamous cell carcinoma (CSCC), yet the underlying mechanism remains unconfirmed. In this study, we show that midkine (MDK) was highly expressed in CSCC and overexpression of MDK was associated with CSCC LNM. Functional investigations demonstrated that MDK promoted LNM by enhancing proliferation, migration and invasion capacity of cervical cancer cells, facilitating lymphangiogenesis and down-regulating the expression of tight junction proteins of human lymphatic endothelial cells (HLECs). MDK exerted these biological effects by interacting with Syndecan-1 and activating PI3K/AKT and p38 MAPK pathways. A retrospective study showed that s-MDK was relate2024-01-01T00:00:00Z2024 Jul2026-05-26T14:04:01.794Z2025-06-01T01:17:52.384ZS-EPMC112610163904005210.1016/j.isci.2024.110077