Learning from Hypoxia Signaling: A Working Group Meeting of the European COST Action TD 0901,Bilbao,Spain,April 18 to 20,2012

L earning from Hypoxia Signaling provided a unique framework to discover the most recent progress related to hypoxia signaling. The meeting started with a session dedicated to hypoxia sensing and signaling. The first speech focused on a new Drosophila 2-oxoglutarate-dependent dioxygenase, called Sudestada (Sda), which has been identified and shown to control cell growth (Wappner P). Moving to mammalian systems, the role of nitric oxide and reactive oxygen species (ROS) as regulators of the dioxygenases, independently of oxygen tension, was further discussed (Fandrey J). In addition, the levels and the localization of these enzymes were shown to modulate overall cellular hydroxylase activity and thus, HIF activation. The session continued with talks elucidating the hypoxic pathway: i) CA IX (Kopacek J); ii) Urotensin-II (Görlach A), reported as a new player involved in disorders associated with angiogenesis; iii) miR-155 (Bruning U), shown to limit HIF activity in a negative feed-back loop by targeting the HIF1α 3’UTR; and iv) miR-127 (Aguado-Fraile E), induced in proximal tubular cells during ischemia/reperfusion and targeting KIF3B. Furthermore, a novel oxygen-binding globin, called androglobin, whose expression is reduced in infertile men's testis was reported (Hoogewijs D). An outstanding work showing the impact of hypoxia in tumor cell dynamics in live chicken embryos closed the session (Herrmann A).

The effects of hypoxia in stem cells focused the second session. The role of acidosis within the glioblastoma stem cells niche (Filatova A) was highlighted, as well as endothelin-1, a carotid body niche factor, promoting CB stem cells (Pardal, R). In addition, the impact of HIF1α and HIF2α in human HSC and leukemic stem cells (Bonnet D) and the relationship of HSC with the immune status (Serebrovskaya, T) were analyzed. Furthermore, hypoxia was shown to increase the stem cell population in normal and tumorigenic human breast (Vivanco, M). The impact of embryonic hypoxia on cardiovascular progenitors was further reported.

The link between hypoxia and cellular metabolism was also addressed. In this context, interesting talks were presented related to: i) the molecular mechanism underlying FH (fumarate hydratase)-associated oncogenesis (Pollard P); ii) the specific role of PML in fatty acid oxidation and the implications in breast cancer (Carracedo A); and iii) hexokinase II functioning as a molecular switch governing cellular fate depending on the metabolic state (Mergenthaler P). An original study of muscle signaling (measured in the vastus lateralis muscle biopsies from volunteers) in response to sprint exercise was further reported (Morales-Alamo D). Finally, the role of Mitofusin-2 (Mfn-2) in mitochondrial fusion and metabolic homeostasis was discussed (Zorzano A).

Hypoxia being a characteristic feature of advanced tumors, a series of presentations was dedicated to explore cancer progression and response to therapies. The notion and biological and clinical consequences of tumor hypoxia subtypes (acute, chronic, and hypoxemic hypoxia) were highlighted (Vaupel P). Then, the role of CAIX, that regulates pH, and particularly CAIX phosphorylation was described (Pastorekova S). The impact of TMEM45A in hypoxia-induced resistance to taxol and etoposide (Michiels C), as well as a new family of HIF inhibitors (Sánchez-Puelles JM) were also reported. Afterwards, the beneficial and detrimental effects of anti-angiogenic therapies were discussed (Casanova O). The understanding of the adaptation to anti-angiogenic therapies is indeed a key factor to improve treatment efficacy and avoid the negative side effects. The role of miR-200a (induced by oxidative stress and targeting p38), which promotes tumor growth and sensitizes tumors to treatment, was also reported (Mechta-Grigoriou F). Although hypoxia is mostly linked to cancer, there are additional diseases where hypoxia is present. Hence, the implication of scavenger receptors in atherosclerosis (Crucet M) and PHD2 in ventilatory acclimatisation (Bishop T) were a matter of discussion. The meeting ended with a talk focused on the consequences and side effects of the use of pan-PHD inhibitors (Maxwell P), justifying and encouraging all of us to continue working in this exciting field.

As a result of the addressed topics and the quality of most of the presentations, the working group meeting Learning from Hypoxia Signaling was a full success and represented an exceptional platform for intense discussion that lasted deep into the night. A highlight was the extensive unpublished data revealed by speakers. The number of participants was relatively small, and this allowed an excellent and personalized interaction between researchers, including younger ones. For certain, several collaborations will result from this interesting meeting.