LRP8 drives cervical cancer lymph node metastasis by promoting epithelial-mesenchymal transition and VEGF-C secretion.
4 affiliations
- 1Laboratory Animal Center, Dalian Medical University, Dalian, 116044, China.
- 2Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Dalian Medical University, Dalian, 116044, China.
- 3Laboratory Animal Center, Dalian Medical University, Dalian, 116044, China. [email protected].
- 4Laboratory Animal Center, Dalian Medical University, Dalian, 116044, China. [email protected].
Abstract
Cervical cancer (CCa) patients with lymph node metastasis (LNM) have poor outcomes and limited therapeutic options. This study investigated the expression, function, and mechanisms of low-density lipoprotein receptor-related protein 8 (LRP8) in CCa-associated LNM. LRP8 expression in CCa tissues was evaluated through bioinformatics analyses and immunohistochemistry. Gain- and loss-of-function assays were performed to assess the effects of LRP8 on cell migration, invasion, and HLEC tube formation. VEGF-C secretion and cellular cholesterol levels were measured using ELISA and commercial assay kits, respectively. Subcutaneous xenograft and footpad popliteal LNM models were established in nude mice. Transcriptome sequencing and Western blotting were performed to identify downstream signaling pathways. Rescue and inhibition experiments were used to define the roles of PI3K/AKT signaling and cholesterol homeostasis. LRP8 was upregulated in CCa tissues, particularly in LNM-positive cases. Functionally, LRP8 enhanced CCa cell migration and invasion and increased the ability of CCa cell-derived conditioned medium to promote HLEC tube formation. In vivo, LRP8 knockout suppressed tumor growth, tumor-associated lymphangiogenesis, and popliteal LNM. Mechanistically, LRP8 activated PI3K/AKT signaling, which contributed to EMT-associated molecular changes and VEGF-C expression and secretion, as supported by in vitro rescue and inhibition experiments. Cholesterol depletion and supplementation further indicated that LRP8-mediated PI3K/AKT activation was partially dependent on intracellular cholesterol homeostasis. This study suggests that LRP8 contributes to CCa-associated LNM and may serve as a potential prognostic biomarker and therapeutic target.
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BibTeX
@article{tang2026lrp8,
title = {{LRP8 drives cervical cancer lymph node metastasis by promoting epithelial-mesenchymal transition and VEGF-C secretion.}},
author = {Ling Tang and Zijuan Zhou and Guang Zeng and Jingyu Wang},
journal = {Clinical and experimental medicine},
year = {2026},
month = aug,
doi = {10.1007/s10238-026-02271-8},
url = {https://europepmc.org/article/MED/42972171},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - LRP8 drives cervical cancer lymph node metastasis by promoting epithelial-mesenchymal transition and VEGF-C secretion.
AU - Ling Tang
AU - Zijuan Zhou
AU - Guang Zeng
AU - Jingyu Wang
PY - 2026
DA - 2026/08/05
JO - Clinical and experimental medicine
DO - 10.1007/s10238-026-02271-8
UR - https://europepmc.org/article/MED/42972171
AB - Cervical cancer (CCa) patients with lymph node metastasis (LNM) have poor outcomes and limited therapeutic options. This study investigated the expression, function, and mechanisms of low-density lipoprotein receptor-related protein 8 (LRP8) in CCa-associated LNM. LRP8 expression in CCa tissues was evaluated through bioinformatics analyses and immunohistochemistry. Gain- and loss-of-function assays were performed to assess the effects of LRP8 on cell migration, invasion, and HLEC tube formation. VEGF-C secretion and cellular cholesterol levels were measured using ELISA and commercial assay kits, respectively. Subcutaneous xenograft and footpad popliteal LNM models were established in nude mice. Transcriptome sequencing and Western blotting were performed to identify downstream signaling pathways. Rescue and inhibition experiments were used to define the roles of PI3K/AKT signaling and cholesterol homeostasis. LRP8 was upregulated in CCa tissues, particularly in LNM-positive cases. Functionally, LRP8 enhanced CCa cell migration and invasion and increased the ability of CCa cell-derived conditioned medium to promote HLEC tube formation. In vivo, LRP8 knockout suppressed tumor growth, tumor-associated lymphangiogenesis, and popliteal LNM. Mechanistically, LRP8 activated PI3K/AKT signaling, which contributed to EMT-associated molecular changes and VEGF-C expression and secretion, as supported by in vitro rescue and inhibition experiments. Cholesterol depletion and supplementation further indicated that LRP8-mediated PI3K/AKT activation was partially dependent on intracellular cholesterol homeostasis. This study suggests that LRP8 contributes to CCa-associated LNM and may serve as a potential prognostic biomarker and therapeutic target.
SN - 1591-8890
SN - 1591-9528
ER -