Targeting glutamine-addiction and overcoming CDK4/6 inhibitor resistance in human esophageal squamous cell carcinoma

Shuo Qie; Akihiro Yoshida; Stuart Parnham; Natalia Oleinik; Gyda C. Beeson; Craig C. Beeson; Besim Ogretmen; Adam J. Bass; Kwok-Kin Wong; Anil K. Rustgi; J. Alan Diehl

doi:10.1038/s41467-019-09179-w

Nature Communications (Mar 2019)

Targeting glutamine-addiction and overcoming CDK4/6 inhibitor resistance in human esophageal squamous cell carcinoma

Shuo Qie,
Akihiro Yoshida,
Stuart Parnham,
Natalia Oleinik,
Gyda C. Beeson,
Craig C. Beeson,
Besim Ogretmen,
Adam J. Bass,
Kwok-Kin Wong,
Anil K. Rustgi,
J. Alan Diehl

Affiliations

Shuo Qie: Department of Biochemistry and Molecular Biology, Hollings Cancer Center, Medical University of South Carolina
Akihiro Yoshida: Department of Biochemistry and Molecular Biology, Hollings Cancer Center, Medical University of South Carolina
Stuart Parnham: Department of Biochemistry and Molecular Biology, Hollings Cancer Center, Medical University of South Carolina
Natalia Oleinik: Department of Biochemistry and Molecular Biology, Hollings Cancer Center, Medical University of South Carolina
Gyda C. Beeson: Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina
Craig C. Beeson: Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina
Besim Ogretmen: Department of Biochemistry and Molecular Biology, Hollings Cancer Center, Medical University of South Carolina
Adam J. Bass: Department of Medical Oncology, Dana-Farber Cancer Institute
Kwok-Kin Wong: Department of Medical Oncology, Dana-Farber Cancer Institute
Anil K. Rustgi: Department of Medicine, Division of Gastroenterology, University of Pennsylvania Perelman School of Medicine
J. Alan Diehl: Department of Biochemistry and Molecular Biology, Hollings Cancer Center, Medical University of South Carolina

DOI: https://doi.org/10.1038/s41467-019-09179-w
Journal volume & issue: Vol. 10, no. 1
pp. 1 – 15

Abstract

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A subset of esophageal squamous cell carcinoma harbors dysregulated Fbxo4- cyclin D1 axis. Here, the authors show that the dysregulation of Fbxo4-cyclin D1 leads to mitochondrial dysfunction and glutamine addiction rendering these tumors susceptible to metabolic inhibitors even when resistant to CDK4/6 inhibitors.

Published in Nature Communications

ISSN: 2041-1723 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science
Website: https://www.nature.com/ncomms/

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