RT info:eu-repo/semantics/article
T1 The cancer cell oxygen sensor PHD2 promotes metastasis via activation of cancer-associated fibroblasts
A1 Hernández Fernaud, Juan Ramón
A1 Kuchnio, Anna
A1 Moens, Stijn
A1 Bruning, Ulrike
A1 Kuchnio, Karol
A1 Cruys, Bert
A1 Thienpont, Bernard
A1 Broux, Michaël
A1 Ungureanu, Andreea Alexandra
A1 Oliveira, Rodrigo Leite de
A1 Bruyère, Françoise
A1 Cuervo, Henar
A1 Manderveld, Ann
A1 Carton, An
A1 Zanivan, Sara
A1 Bartic, Carmen
A1 Foidart, Jean-Michel
A1 Noel, Agnes
A1 Vinckier, Stefan
A1 Lambrechts, Diether
A1 Carmeliet, Peter
A2 BioquímicaMicrobiología, Biología Celular y Genética
A2 The Beatson Institute for Cancer ResearchGlasgow, UK
AB Several questions about the role of the oxygen sensor prolyl-hydroxylase 2 (PHD2) in cancer have not beenaddressed.First, the role of PHD2inmetastasis has not been studied in a spontaneous tumor model. Here, we show that global PHD2 haplodeficiency reduced metastasis without affecting tumor growth. Second, it is unknown whether PHD2 regulates cancer by affecting cancer-associated fibroblasts (CAFs). We show that PHD2 haplodeficiency reduced metastasis via two mechanisms: (1) by decreasing CAF activation, matrix production, and contraction byCAFs,aneffectthatsurprisingly relied on PHD2 deletion in cancer cells, but not in CAFs; and (2) by improving tumor vessel normalization. Third, the effect of concomitant PHD2 inhibition in malignant and stromal cells (mimicking PHD2 inhibitor treatment) is unknown. We show that global PHD2 haplodeficiency, induced not only before but also after tumor onset, impaired metastasis. These f indings warrant investigation of PHD2’s therapeutic potential.
YR 2015
FD 2015
LK http://riull.ull.es/xmlui/handle/915/38829
UL http://riull.ull.es/xmlui/handle/915/38829
LA en
DS Repositorio institucional de la Universidad de La Laguna
RD 26-dic-2024