Hypoxia, notch signalling, and prostate cancer

Abstract

The notch signalling pathway is involved in differentiation, proliferation, angiogenesis, vascular remodelling, and apoptosis. Deregulated expression of notch receptors, ligands, and targets is observed in many solid tumours, including prostate cancer. Hypoxia is a common feature of prostate tumours, leading to increased gene instability, reduced treatment response, and increased tumour aggressiveness. The notch signalling pathway is known to regulate vascular cell fate and is responsive to hypoxia-inducible factors. Evidence to date suggests similar, therapeutically exploitable, behaviour of notch-activated and hypoxic prostate cancer cells.

Association Between Hypoxia-Inducible Factor-2α (HIF-2α) Expression and Colorectal Cancer and Its Prognostic Role: a Systematic Analysis

“…Tumor hypoxia is a pathological hallmark that may be correlated with metabolism, the activation of cell signaling, angiogenesis, differentiation, necrosis or cell apoptosis, tumor development and aggressiveness, etc [10][11][12].. Additionally, tumor hypoxia can have an adverse impact on the prognosis of some cancers (i.e., invasive breast cancer or cervical cancer) and the efficacy of chemo-and radiotherapy [13,14]. Hypoxia-inducible factor-2α (HIF-2α), also named the endothelial PAS domain protein 1 (EPAS1), a member of the hypoxia-inducible factors (HIFs), is an essential marker, which mediates the transcriptional response to hypoxia stress [15][16][17].…”

Activation of Notch pathway is linked with epithelial-mesenchymal transition in prostate cancer cells

“…13,14 Thus, ICN forms a complex with CSL (CBF1/Su(H)/Lag-1) and triggers the transcription of its targets such as cyclin D, Hey family and Hes (hairy enhancer of split) family. 15 Deregulated Notch signaling has been observed in a variety of human cancers including prostate cancer. [16][17][18][19] For example, Jagged-1 expression is associated with prostate cancer metastasis and recurrence.…”

Androgen Receptor Promotes the Oncogenic Function of Overexpressed Jagged1 in Prostate Cancer by Enhancing Cyclin B1 Expression via Akt Phosphorylation

“…Many cell signaling pathways play different roles in the development and progression of prostate cancer, such as NF-kB, JAK/STAT, MAPK, Wnt, PI3K/Akt, and Notch signaling. Among these, the Notch signaling pathway, which is present in most multicellular organisms, plays a role in cancer metastasis by governing embryonic development, maintaining tumor stemness, modulating the epithelial-to-mesenchymal transition (EMT), and affecting tumor angiogenesis processes (12)(13)(14). Several studies have demonstrated that the Notch signaling pathway is required for prostatic growth and plays a key role in the progression and metastasis of prostate cancer (15)(16)(17).…”