Tenascin-C is an extracellular matrix molecule that drives progression of many types of human cancer but the basis for its actions remain obscure. In this study, we describe a cell-autonomous signaling mechanism explaining how tenascin-C promotes cancer cell migration in the tumor microenvironment. In a murine xenograft model of advanced human osteosarcoma, tenascin-C and its receptor integrin α9β1 were determined to be essential for lung metastasis of tumor cells. We determined that activation of this pathway also reduced tumor cell-autonomous expression of target genes for the transcription factor YAP. In clinical specimens, a genetic signature comprising four YAP target genes represents prognostic impact. Taken together, our results illuminate how tumor cell deposition of tenascin-C in the tumor microenvironment promotes invasive migration and metastatic progression.
Among metabolic rearrangements occurring in cancer cells, lipid metabolism alteration has become a hallmark, aimed at sustaining accelerated proliferation. In particular, fatty acids (FAs) are dramatically required by cancer cells as signalling molecules and membrane building blocks, beyond bioenergetics. Along with de novo biosynthesis, free FAs derive from dietary sources or from intracellular lipid droplets, which represent the storage of triacylglycerols (TAGs). Adipose triglyceride lipase (ATGL) is the rate-limiting enzyme of lipolysis, catalysing the first step of intracellular TAGs hydrolysis in several tissues. However, the roles of ATGL in cancer are still neglected though a putative tumour suppressor function of ATGL has been envisaged, as its expression is frequently reduced in different human cancers (e.g., lung, muscle, and pancreas). In this review, we will introduce lipid metabolism focusing on ATGL functions and regulation in normal cell physiology providing also speculative perspectives on potential non-energetic functions of ATGL in cancer. In particular, we will discuss how ATGL is implicated, mainly through the peroxisome proliferator-activated receptor-α (PPAR-α) signalling, in inflammation, redox homoeostasis and autophagy, which are well-known processes deregulated during cancer formation and/or progression.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.