MTOR signaling orchestrates stress-induced mutagenesis, facilitating adaptive evolution in cancer-Reference-Cited by-同舟云学术

MTOR signaling orchestrates stress-induced mutagenesis, facilitating adaptive evolution in cancer

Published:2020-06-05 Issue:6495 Volume:368 Page:1127-1131
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Cipponi Arcadi¹²^ORCID,Goode David L.³⁴^ORCID,Bedo Justin⁵⁶⁷^ORCID,McCabe Mark J.²⁸^ORCID,Pajic Marina¹²^ORCID,Croucher David R.¹²^ORCID,Rajal Alvaro Gonzalez¹^ORCID,Junankar Simon R.¹²^ORCID,Saunders Darren N.⁹^ORCID,Lobachevsky Pavel³^ORCID,Papenfuss Anthony T.⁵⁶⁷¹⁰^ORCID,Nessem Danielle¹^ORCID,Nobis Max¹²^ORCID,Warren Sean C.¹²^ORCID,Timpson Paul¹²,Cowley Mark²⁸^ORCID,Vargas Ana C.¹¹,Qiu Min R.²¹²,Generali Daniele G.¹³¹⁴,Keerthikumar Shivakumar³⁴^ORCID,Nguyen Uyen¹^ORCID,Corcoran Niall M.¹⁵¹⁶¹⁷^ORCID,Long Georgina V.¹⁸¹⁹²⁰²¹^ORCID,Blay Jean-Yves²²²³^ORCID,Thomas David M.¹²^ORCID

Affiliation:

1. The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.

2. St. Vincent's Clinical School, University of New South Wales, Sydney, NSW, Australia.

3. Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.

4. Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, VIC, Australia.

5. Bioinformatics Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.

6. Department of Computing and Information Systems, the University of Melbourne, Parkville, VIC, Australia.

7. Peter MacCallum Cancer Centre, Parkville, VIC, Australia.

8. Kinghorn Centre for Clinical Genomics, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.

9. School of Medical Sciences, University of New South Wales, NSW, Australia.

10. Department of Medical Biology, University of Melbourne, Melbourne, VIC, Australia.

11. Douglass Hanly Moir Pathology, Turramurra, NSW, Australia.

12. Anatomical and Molecular Oncology Pathology, SYDPATH, St. Vincent’s Hospital, Darlinghurst, NSW, Australia.

13. Department of Medical, Surgery and Health Sciences, University of Trieste, Trieste, Italy.

14. Breast Cancer Unit and Translational Research Unit, ASST Cremona, Cremona, Italy.

15. Division of Urology, Royal Melbourne Hospital, Parkville, VIC, Australia.

16. Department of Urology, Peninsula Health, Frankston, VIC, Australia.

17. Department of Surgery, University of Melbourne, VIC, Australia.

18. Melanoma Institute Australia, Wollstonecraft, NSW, Australia.

19. The University of Sydney, Sydney, NSW, Australia.

20. Royal North Shore Hospital and Mater Hospital, Sydney, NSW, Australia.

21. Crown Princess Mary Cancer Centre Westmead Hospital, Sydney, NSW, Australia.

22. Centre Leon Berard and Université Claude Bernard Lyon, Lyon, France.

23. UNICANCER, Paris, France.

Abstract

How cancer cells adapt to stress Bacteria adapt to harsh conditions such as antibiotic exposure by acquiring new mutations, a process called stress-induced mutagenesis. Cipponi et al. investigated whether similar programs of mutagenesis play a role in the response of cancer cells to targeted therapies. Using in vitro models of intense drug selection and genome-wide functional screens, the authors found evidence for an analogous process in cancer and showed that it is regulated by the mammalian target of rapamycin (mTOR) signaling pathway. This pathway appears to mediate a stress-related switch to error-prone DNA repair, resulting in the generation of mutations that facilitate the emergence of drug resistance. Science , this issue p. 1127

Funder

Cancer Australia

Australian national health and medical research council

Girgenshon Foundation

MEDnoTE Spin-Off University of Trieste

Australian national health and medical resesrach council

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Reference72 articles.

1. A genetic model for colorectal tumorigenesis