DOI: 10.1101/488304Dec 6, 2018Paper

Podoplanin interaction with caveolin-1 promotes tumour cell migration and invasion

BioRxiv : the Preprint Server for Biology
Luisa Pedro, Jacqueline D Shields

Abstract

Podoplanin, a highly O-glycosylated type-1 transmembrane glycoprotein, found in lymphatic endothelial cells, podocytes, alveolar epithelial cells and lymph node fibroblasts is also expressed by tumour cells, and is correlated with more aggressive disease. Despite numerous studies documenting podoplanin expression, the mechanisms underlying its tumour-promoting functions remain unclear. Using a murine melanoma cell line that endogenously expresses podoplanin, we demonstrate interactions with proteins necessary for cytoskeleton reorganization, adhesion and matrix degradation, and endocytosis/receptor recycling but also identify a novel interaction with caveolin-1. We generated a panel of podoplanin and caveolin-1 variants to determine the molecular interactions and functional consequences of these interactions. Complementary in vitro and in vivo systems confirmed the existence of a functional cooperation in which surface expression of both full length, signalling competent podoplanin and caveolin-1 are necessary to induce directional migration and invasion, which is executed via PAK1 and ERK1 pathways. Our findings establish that podoplanin signalling mediates the invasive properties of melanoma cells in a caveolin-1 dependent ma...Continue Reading

Related Concepts

Tissue Adhesions
Cytoskeleton
Endocytosis
Fibroblasts
Melanoma
Neoplasm Metastasis
Neoplasms
Cell Line, Tumor
Surface
Endothelial Cells

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