biostudies-literatureXiong GU.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)U.S. Department of Health & Human Services | NIH | National Cancer InstituteDOD | Congressionally Directed Medical Research ProgramsNCI NIH HHSDOD | Congressionally Directed Medical Research Programs (CDMRP)4456https://www.ebi.ac.uk/biostudies/studies/S-EPMC6203834biostudies-literatureUnknown9(1)Collagen prolyl 4-hydroxylase (P4H) expression and collagen hydroxylation in cancer cells are necessary for breast cancer progression. Here, we show that P4H alpha 1 subunit (P4HA1) protein expression is induced in triple-negative breast cancer (TNBC) and HER2 positive breast cancer. By modulating alpha ketoglutarate (α-KG) and succinate levels P4HA1 expression reduces proline hydroxylation on hypoxia-inducible factor (HIF) 1α, enhancing its stability in cancer cells. Activation of the P4HA/HIF-1 axis enhances cancer cell stemness, accompanied by decreased oxidative phosphorylation and reactive oxygen species (ROS) levels. Inhibition of P4HA1 sensitizes TNBC to the chemotherapeutic agent docetaxel and doxorubicin in xenografts and patient-derived models. We also show that increased P4HA1 eNature communicationsCollagen prolyl 4-hydroxylase 1 is essential for HIF-1α stabilization and TNBC chemoresistance.PMC6203834R01 CA109136P30 CA177558R21 CA209045R01 CA223164CA207772, CA215095, CA209045R01 CA215095W81XWH-15-1-0052R01 CA207772O'Connor KChen JScott TLSamayoa LMXu RStewart RLLane ANXiong GGao TfalseCollagen prolyl 4-hydroxylase 1 is essential for HIF-1α stabilization and TNBC chemoresistance.Collagen prolyl 4-hydroxylase (P4H) expression and collagen hydroxylation in cancer cells are necessary for breast cancer progression. Here, we show that P4H alpha 1 subunit (P4HA1) protein expression is induced in triple-negative breast cancer (TNBC) and HER2 positive breast cancer. By modulating alpha ketoglutarate (α-KG) and succinate levels P4HA1 expression reduces proline hydroxylation on hypoxia-inducible factor (HIF) 1α, enhancing its stability in cancer cells. Activation of the P4HA/HIF-1 axis enhances cancer cell stemness, accompanied by decreased oxidative phosphorylation and reactive oxygen species (ROS) levels. Inhibition of P4HA1 sensitizes TNBC to the chemotherapeutic agent docetaxel and doxorubicin in xenografts and patient-derived models. We also show that increased P4HA1 e2018-01-01T00:00:00Z2018 Oct2026-05-05T23:06:30.544Z2026-04-07T22:06:07.114ZS-EPMC62038343036704210.1038/s41467-018-06893-9