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Hypoxia-inducible factor 1 (HIF-1), principal component of HIF-1 pathway, is a transcriptional activator induced by hypoxia, and a modulator of oxygen homeostasis and physiological responses (1).

In hypoxic conditions, HIF-1 plays an essential role in the adaptation of cells and organs to changes related to the presence of oxygen (5), and it is required to maintain the pluripotency and survival of stem cells under hypoxic conditions (6).


Hypoxia inducible factor-1 α (HIF-1α) is the key responder adapted to tumor hypoxia. Under hypoxia conditions, HIF-1α signaling is activated and responsible for cell biology associated with metabolism, inflammation, vascular homeostasis and tumorigenesis (3). HIF-1 regulates tumor biological behavior by influencing apoptotic/proliferative activity, vasomotor function, energy metabolism, and angiogenesis (4).

Previous research indicates that hypoxia increases the population of lung cancer stem cells resistant to gefitinib in EGFR mutation-positive NSCLC, and the HIF-1 signaling pathway is activated in EGFR-TKI-resistant lung cancer cells (2).
HIF-1α activation is related to the development of multidrug resistance and hypoxia-induced EMT in tumor cells (4). Moreover, recent findings suggest that HIF-1α-activated autophagy is a crucial factor in the promotion of cell survival under the distressed microenvironment, thereby leading to the chemo-/radioresistance (7).


The oncogenic and tumor suppressive activity of HIF in tumor and stromal cells (5)

(1) Fu X et Zhang F. Role of the HIF-1 signaling pathway in chronic obstructive pulmonary disease. Exp Ther Med. (2018);16(6):4553-4561.
(2) Jin Q et al. Hypoxia-inducible factor-1 signaling pathway influences the sensitivity of HCC827 cells to gefitinib. Oncol Lett. (2019);17(4):4034-4043.
(3) Li H et al. Targeting HIF-1α signaling pathway for gastric cancer treatment. Pharmazie.(2019);74(1):3-7.
(4) Qin Y et al. Salidroside improves the hypoxic tumor microenvironment and reverses the drug resistance of platinum drugs via HIF-1α signaling pathway. EBioMedicine. (2018);38:25-36.
(5) Huang Y et al. Hypoxia inducible factor (HIF) in the tumor microenvironment: friend or foe? Sci China Life Sci. (2017);60(10):1114-1124.
(6) Lee HJ et al. Role of HIF1α Regulatory Factors in Stem Cells. Int J Stem Cells. (2019 );12(1):8-20.
(7) Xia Y et al. The role of HIF-1α in chemo-/radioresistant tumors. Onco Targets Ther. (2018); 11: 3003–3011.


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You can check the biomarker list included in this pathway, see below:
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