TY - JOUR
T1 - Ubiquitous Aberration in Cholesterol Metabolism across Pancreatic Ductal Adenocarcinoma
AU - Gunda, Venugopal
AU - Genaro-Mattos, Thiago C.
AU - Kaushal, Jyoti B.
AU - Chirravuri-Venkata, Ramakanth
AU - Natarajan, Gopalakrishnan
AU - Mallya, Kavita
AU - Grandgenett, Paul M.
AU - Mirnics, Karoly
AU - Batra, Surinder K.
AU - Korade, Zeljka
AU - Rachagani, Satyanarayana
N1 - Funding Information:
Acknowledgments: The authors are thankful to Dr Michel Ouellette for providing HPNE cells and the funding from the National Institutes of Health and the National Cancer Institute R01 CA247763, R21 CA238953, MH110636, and P01 CA217798.
Funding Information:
Funding: The authors obtained funding from the National Institutes of Health and the National Cancer Institute R01 CA247763, R21 CA238953, MH110636, and P01 CA217798.
Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/1
Y1 - 2022/1
N2 - Pancreatic cancer (PC) is characterized by metabolic deregulations that often manifest as deviations in metabolite levels and aberrations in their corresponding metabolic genes across the clinical specimens and preclinical PC models. Cholesterol is one of the critical metabolites supporting PC, synthesized or acquired by PC cells. Nevertheless, the significance of the de novo cholesterol synthesis pathway has been controversial in PC, indicating the need to reassess this pathway in PC. We utilized preclinical models and clinical specimens of PC patients and cell lines and utilized mass spectrometry-based sterol analysis. Further, we also performed in silico analysis to corroborate the significance of de novo cholesterol synthesis pathway in PC. Our results demonstrated alteration in free sterol levels, including free cholesterol, across in vitro, in vivo, and clinical specimens of PC. Especially, our sterol analyses established consistent alterations in free cholesterol across the different PC models. Overall, this study demonstrates the significance and consistency in deviation of cholesterol synthesis pathway in PC while showing the aberrations in sterol metabolite intermediates and the related genes using preclinical models, in silico platforms, and the clinical specimens.
AB - Pancreatic cancer (PC) is characterized by metabolic deregulations that often manifest as deviations in metabolite levels and aberrations in their corresponding metabolic genes across the clinical specimens and preclinical PC models. Cholesterol is one of the critical metabolites supporting PC, synthesized or acquired by PC cells. Nevertheless, the significance of the de novo cholesterol synthesis pathway has been controversial in PC, indicating the need to reassess this pathway in PC. We utilized preclinical models and clinical specimens of PC patients and cell lines and utilized mass spectrometry-based sterol analysis. Further, we also performed in silico analysis to corroborate the significance of de novo cholesterol synthesis pathway in PC. Our results demonstrated alteration in free sterol levels, including free cholesterol, across in vitro, in vivo, and clinical specimens of PC. Especially, our sterol analyses established consistent alterations in free cholesterol across the different PC models. Overall, this study demonstrates the significance and consistency in deviation of cholesterol synthesis pathway in PC while showing the aberrations in sterol metabolite intermediates and the related genes using preclinical models, in silico platforms, and the clinical specimens.
KW - Dhcr24
KW - Dhcr7
KW - Free cholesterol
KW - PDAC
KW - Sterol analysis
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U2 - 10.3390/metabo12010047
DO - 10.3390/metabo12010047
M3 - Article
C2 - 35050168
AN - SCOPUS:85122748226
SN - 2218-1989
VL - 12
JO - Metabolites
JF - Metabolites
IS - 1
M1 - 47
ER -