Autocrine and paracrine effects of MDK promote lymph node metastasis of cervical squamous cell carcinoma
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Updated: Jun 20, 2025

Author Spotlight: A Model to Study the Systemic and Local Dynamics of CD8+ T Cells During LN Metastasis
Published on: January 26, 2024
He Fei1, Tong Chen2, Hua Jiang3,4
1Department of Gynecology, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai 200240, China.
Abstract:
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 related to LNM. s-MDK combined with serum-squamous cell carcinoma antigen(s-SCCA) improved the diagnostic accuracy of CSCC LNM. These findings established a new mechanism of LNM and highlighted MDK as a candidate tumor biomarker and therapeutic target in CSCC.
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