Nature Communications (Mar 2022)
A non-dividing cell population with high pyruvate dehydrogenase kinase activity regulates metabolic heterogeneity and tumorigenesis in the intestine
- Carlos Sebastian,
- Christina Ferrer,
- Maria Serra,
- Jee-Eun Choi,
- Nadia Ducano,
- Alessia Mira,
- Manasvi S. Shah,
- Sylwia A. Stopka,
- Andrew J. Perciaccante,
- Claudio Isella,
- Daniel Moya-Rull,
- Marianela Vara-Messler,
- Silvia Giordano,
- Elena Maldi,
- Niyati Desai,
- Diane E. Capen,
- Enzo Medico,
- Murat Cetinbas,
- Ruslan I. Sadreyev,
- Dennis Brown,
- Miguel N. Rivera,
- Anna Sapino,
- David T. Breault,
- Nathalie Y. R. Agar,
- Raul Mostoslavsky
Affiliations
- Carlos Sebastian
- Candiolo Cancer Institute-FPO, IRCCS
- Christina Ferrer
- The Massachusetts General Hospital Cancer Center, Harvard Medical School
- Maria Serra
- Candiolo Cancer Institute-FPO, IRCCS
- Jee-Eun Choi
- The Massachusetts General Hospital Cancer Center, Harvard Medical School
- Nadia Ducano
- Candiolo Cancer Institute-FPO, IRCCS
- Alessia Mira
- Candiolo Cancer Institute-FPO, IRCCS
- Manasvi S. Shah
- Division of Endocrinology, Boston Children’s Hospital
- Sylwia A. Stopka
- Department of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical School
- Andrew J. Perciaccante
- Department of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical School
- Claudio Isella
- Candiolo Cancer Institute-FPO, IRCCS
- Daniel Moya-Rull
- Candiolo Cancer Institute-FPO, IRCCS
- Marianela Vara-Messler
- Department of Oncology, University of Torino
- Silvia Giordano
- Candiolo Cancer Institute-FPO, IRCCS
- Elena Maldi
- Candiolo Cancer Institute-FPO, IRCCS
- Niyati Desai
- Department of Pathology, Massachusetts General Hospital and Harvard Medical School
- Diane E. Capen
- Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School
- Enzo Medico
- Candiolo Cancer Institute-FPO, IRCCS
- Murat Cetinbas
- Department of Pathology, Massachusetts General Hospital and Harvard Medical School
- Ruslan I. Sadreyev
- Department of Pathology, Massachusetts General Hospital and Harvard Medical School
- Dennis Brown
- Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School
- Miguel N. Rivera
- The Massachusetts General Hospital Cancer Center, Harvard Medical School
- Anna Sapino
- Candiolo Cancer Institute-FPO, IRCCS
- David T. Breault
- Division of Endocrinology, Boston Children’s Hospital
- Nathalie Y. R. Agar
- Department of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical School
- Raul Mostoslavsky
- The Massachusetts General Hospital Cancer Center, Harvard Medical School
- DOI
- https://doi.org/10.1038/s41467-022-29085-y
- Journal volume & issue
-
Vol. 13,
no. 1
pp. 1 – 13
Abstract
Metabolic reprogramming upon SIRT6 loss induces tumour formation in the intestine but the mechanism is unclear. Here, the authors show that loss of SIRT6 leads to the expansion of epithelial cells with high pyruvate dehydrogenase kinase activity resulting in enhanced stem cell activity and tumour-initiating potential
