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Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease with a 5-year survival rate of less than 9% and is projected to become the second leading cause of cancer death by 2030
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease with a 5-year survival rate of less than 9% and is projected to become the second leading cause of cancer death by 2030
Recently, an academic paper titled "USP25 promotes pathological HIF-1-driven metabolic reprogramming and is a potential therapeutic target in pancreatic cancer" published in Nature Communications found that USP25 acts as a basic DUB required for PDAC tumor growth and viability.
In the present study, to identify enzymatically active DUBs in PDAC, we developed an analytical pipeline combining ubiquitin-ABPs with mass spectrometry, combining activity-based proteomics with patient-derived PDAC organoids and mice Combined loss-of-function genetic screening
In the present study, to identify enzymatically active DUBs in PDAC, we developed an analytical pipeline combining ubiquitin-ABPs with mass spectrometry, combining activity-based proteomics with patient-derived PDAC organoids and mice Combined loss-of-function genetic screening
Figure USP25 depletion leads to attenuated patient-derived organoid formation, viability, and in vivo PDAC tumor growth
Figure USP25 depletion leads to attenuated patient-derived organoid formation, viability, and in vivo PDAC tumor growthThe study further found that USP25 is a master regulator of glycolysis by regulating the stability and transcriptional activity of hypoxia-inducible factor-1α (HIF-1α)
The study further found that USP25 is a master regulator of glycolysis by regulating the stability and transcriptional activity of hypoxia-inducible factor-1α (HIF-1α)
In conclusion, this study identified USP25 as a potential therapeutic target for pancreatic ductal adenocarcinoma
references:
Nelson, JK, Thin, MZ, Evan, T.
Nelson, JK, Thin, MZ, Evan, T.
et al.
USP25 promotes pathological HIF-1-driven metabolic reprogramming and is a potential therapeutic target in pancreatic cancer.
Nat Commun 13, 2070 (2022).
https://doi.
org/10.
1038/s41467-022-29684-9 https://doi.
org/10.
1038/s41467-022-29684-9
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