AXL promotes lymphangiogenesis by amplifying VEGF-C-mediated AKT pathway.

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Tác giả: Louis Baudin, Sophie Bekisz, Silvia Blacher, Florence Buntinx, Jonathan Deroye, Marine Gautier-Isola, Christine Gilles, Fabrice Gucciardo, Elitsa Ivanova, Alizée Lebeau, Agnès Noël, Sébastien Pirson, Loïc Rouaud, Bernard Staumont, Aline Vanwynsberghe

Ngôn ngữ: eng

Ký hiệu phân loại: 978.02 1800–1899

Thông tin xuất bản: Switzerland : Cellular and molecular life sciences : CMLS , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 681012

Lymphangiogenesis has gained considerable interest due to its established role in cancer progression and dissemination of metastatic cells through lymph nodes. Deciphering the molecular mechanisms that govern lymphangiogenesis within lymph nodes holds promise for revealing novel targetable molecules and pathways to inhibit metastasis. In this study, we revealed a previously unrecognized role of AXL, a tyrosine kinase receptor, in the lymphatic vessel formation. We first validated the expression of AXL in lymphatic endothelial cells (LECs), followed by functional studies using RNA interference and pharmacological inhibition with R428/Bemcentinib. These approaches provided compelling evidence that AXL promotes LEC migration in both 2D and 3D culture systems. Our findings demonstrated that AXL activation was induced by VEGF-C (Vascular Endothelial Growth Factor C) and further amplified downstream signaling via the AKT pathway. In vivo, the role of AXL in lymphatic vessel sprouting was demonstrated using R428 in a model of VEGF-C-induced lymphangiogenesis in lymph nodes. Interestingly, we discovered that AXL was predominantly expressed in MARCO
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