Created: Monday, 10 February 2020 08:04
Serina Cheung Biography:
Serina Cheung is currently a second year MSc student in Dr. Marianne Koritzinsky’s lab. She is investigating the role of p38 mitogen-activation protein kinase in promoting the survival of castration-resistant prostate cancer under hypoxia. She will be presenting this work at the Keystone Symposia Tumor Metabolism conference in Banff, Alberta.
Abstract: Identifying mechanisms that determine sensitivity to p38 MAPK inhibition in castration-resistant prostate cancer
Androgen receptor (AR) signaling is the major driver of castration-resistant prostate cancer (CRPC). Tumor hypoxia increases AR signaling and is associated with treatment resistance. p38 MAP kinase is involved in AR signaling by activating heat shock protein 27, a chaperone for AR translocation. Additionally, the activation of p38 has been found to be an early response to hypoxia. However, the role of p38 in AR signaling under hypoxia in CRPC has not been explored. In this study, we evaluated the role of p38 on AR signaling under hypoxia in CRPC cells. Our results demonstrate that p38 activation is an early response to hypoxia. Hypoxia increased ligand-dependent AR binding to androgen-responsive element and expression of AR target genes. Pharmacological p38 inhibition decreased the hypoxia-induced increase in AR activity. Additionally, pharmacological inhibition and siRNA knockdown of p38 decreased cell proliferation and survival in prostate cancer cells dependent on AR signaling for survival. These results suggest further investigation of p38 inhibition as a therapeutic strategy to disrupt AR signaling in CPRC.
Read more: Travel Grant Awardees
Created: Wednesday, 22 November 2017 15:16
Hanahan and Weinberg’s seminal papers on the Hallmarks of Cancer describe how cancer cells accommodate the frenzied growth characteristic of tumors. Low oxygen is eminently characteristic of tumors, and in this hypoxic environment, metabolism is reprogrammed to satisfy energetic and synthetic needs of the cells.
Read more: Hypoxia and the Hallmarks of Cancer: Metabolic Reprogramming