2. Academic Validation
  3. Autocrine and paracrine effects of MDK promote lymph node metastasis of cervical squamous cell carcinoma

Autocrine and paracrine effects of MDK promote lymph node metastasis of cervical squamous cell carcinoma

  • iScience. 2024 May 22;27(7):110077. doi: 10.1016/j.isci.2024.110077.
He Fei 1,  Tong Chen 2,  Hua Jiang 3 4
Affiliations

Affiliations

  • 1 Department of Gynecology, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai 200240, China.
  • 2 Department of Hematology, Huashan Hospital, Fudan University, Shanghai 200040, China.
  • 3 Department of Gynecology, Obstetrics & Gynecology Hospital, Fudan University, Shanghai 200011, China.
  • 4 Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai 200011, China.
PMID: 39040052 DOI: 10.1016/j.isci.2024.110077
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.

Keywords

Biological sciences; Cancer; Systems biology.

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