Detalle de: lnc RNAs, hypoxia and metastasis

In a variety of pathophysiological conditions oxygen demand exceeds its supply, leading to a compromising condition referred to as hypoxia, which triggers complex adaptive mechanisms mediated primarily through transcriptional reprogramming by hypoxia inducible factors (HIFs). Solid tumors are an example of this condition, as deregulated proliferation generates oxygen deficient microenvironments to which cancer cells need to adapt. Among the adaptive processes, the growth of new vessels (angiogenesis) and metabolic reprogramming are central to cope with low oxygen tension. However, in the context of solid tumors, hypoxic areas perpetuate and expand due to the aberrant activation of angiogenesis which gives rise to abnormal tumor vessels and a dysfunctional tumor vasculature. In fact, the prognostic significance of hypoxic regions is well recognized and tumor hypoxia is causally associated with resistance to therapy. Additionally, hypoxia induces metastasis through regulation of several critical processes implicated in the complex metastatic cascade, especially epithelial-mesenchymal transition and cancer stem cell renewal. Recent studies have implicated HIF target genes in nearly every step of the metastatic process; however, the precise molecular and cellular mechanisms underlying hypoxia-induced metastatic dissemination are just beginning to be uncovered.