AUTHOR=Laitala Anu , Erler Janine T. TITLE=Hypoxic Signalling in Tumour Stroma JOURNAL=Frontiers in Oncology VOLUME=8 YEAR=2018 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2018.00189 DOI=10.3389/fonc.2018.00189 ISSN=2234-943X ABSTRACT=

Hypoxia is a common feature in solid tumors and is associated with cancer progression. The main regulators of the hypoxic response are hypoxia-inducible transcription factors (HIFs) that guide the cellular adaptation to hypoxia by gene activation. The actual oxygen sensing is performed by HIF prolyl hydroxylases (PHDs) that under normoxic conditions mark the HIF-α subunit for degradation. Cancer progression is not regulated only by the cancer cells themselves but also by the whole tumor microenvironment, which consists of cellular and extracellular components. Hypoxic conditions also affect the stromal compartment, where stromal cells are in close contact with the cancer cells. The important function of HIF in cancer cells has been shown by many animal models and described in hundreds of reviews, but less in known about PHDs and even less PHDs in stromal cells. Here, we review hypoxic signaling in tumors, mainly in the tumor stroma, with a focus on HIFs and PHDs.