Regulation of HIFs in Cancer Cells

Dear Colleagues,

Hypoxia, a condition in which cells are exposed to reduced oxygen levels, is implicated in physiological processes, such as life in high altitude and intense exercise, but also in pathologic conditions, including ischemia, inflammatory disorders, pulmonary diseases, renal diseases, and cancer. Cancer cells under hypoxia exhibit significant changes in gene expression patterns in order to facilitate their adaptation under the hypoxic microenvironment. This transcriptional reprogramming is mainly coordinated by Hypoxia-Inducible transcription Factors (HIF) and allows cells to alter their metabolism, proliferate, and acquire resistance to death. However, it also facilitates processes such as angiogenesis and vascularization of the tumor, invasion, and metastasis.

HIFs are a small family of heterodimeric transcription factors comprising three distinct isoforms (HIF-1, HIF-2, HIF-3), and consist of an oxygen-regulated HIF-α subunit and a stably expressed HIF-β subunit or ARNT (Aryl hydrocarbon Receptor Nuclear Translocator). HIF-α oxygen-regulated subunits are often overexpressed in human cancers, not only by local hypoxia but also by oncogenic mutations (as in VHL) or overactivation of signaling pathways such as PI3K/AKT/mTOR or Ras/ERK1/2 that stimulate HIF-α expression and/or HIF transcriptional activity. In addition, the overexpression of HIF-α is observed in many cancers and is strongly correlated with poor patient prognosis and resistance to conventional therapy.

Thus, HIFs represent an attractive target for anticancer therapy and a global effort is underway to find strategies to control and modulate HIF activity for therapeutic purposes. Recent preclinical models and clinical studies have shown the prospects of inhibiting HIF in poorly oxygenated cancer cells; however, the full potential of HIF inhibition may be revealed when it is combined with other treatments as a tool to fight cancer.

Therefore, in order to develop new tools that effectively impact hypoxic cancer cells and limit tumor growth, it is important to elucidate the mechanistic details of HIF regulation in cancer cells and gain new knowledge on the contribution of various HIF isoforms in different types of cancer.

Dr. Panagiotis Liakos
Dr. Ilias Mylonis
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.