Chronic TGF-β exposure drives stabilized EMT, tumor stemness, and cancer drug resistance with vulnerability to bitopic mTOR inhibition

Yoko Katsuno; Dominique Stephan Meyer; Ziyang Zhang; Kevan M. Shokat; Rosemary J. Akhurst; Kohei Miyazono; Rik Derynck

doi:10.1126/scisignal.aau8544

Research ArticleCancer

Chronic TGF-β exposure drives stabilized EMT, tumor stemness, and cancer drug resistance with vulnerability to bitopic mTOR inhibition

View ORCID ProfileYoko Katsuno ¹,²,³,
View ORCID ProfileDominique Stephan Meyer ⁴,
View ORCID ProfileZiyang Zhang⁵,
View ORCID ProfileKevan M. Shokat ⁵,
View ORCID ProfileRosemary J. Akhurst ²,⁴,⁶,
View ORCID ProfileKohei Miyazono ³, and
View ORCID ProfileRik Derynck ¹,²,⁴,⁶,*

¹Department of Cell and Tissue Biology, University of California at San Francisco, San Francisco, CA 94143, USA.
²Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California at San Francisco, San Francisco, CA 94143, USA.
³Department of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
⁴Helen Diller Family Comprehensive Cancer Center, University of California at San Francisco, San Francisco, CA 94143, USA.
⁵Department of Cellular and Molecular Pharmacology and Howard Hughes Medical Institute, University of California at San Francisco, San Francisco, CA 94143, USA.
⁶Department of Anatomy, University of California at San Francisco, San Francisco, CA 94143, USA.

↵*Corresponding author. Email: rik.derynck{at}ucsf.edu

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Science Signaling 26 Feb 2019:
Vol. 12, Issue 570, eaau8544
DOI: 10.1126/scisignal.aau8544

Yoko Katsuno

1Department of Cell and Tissue Biology, University of California at San Francisco, San Francisco, CA 94143, USA.

2Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California at San Francisco, San Francisco, CA 94143, USA.

3Department of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.

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Dominique Stephan Meyer

4Helen Diller Family Comprehensive Cancer Center, University of California at San Francisco, San Francisco, CA 94143, USA.

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Ziyang Zhang

5Department of Cellular and Molecular Pharmacology and Howard Hughes Medical Institute, University of California at San Francisco, San Francisco, CA 94143, USA.

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Kevan M. Shokat

5Department of Cellular and Molecular Pharmacology and Howard Hughes Medical Institute, University of California at San Francisco, San Francisco, CA 94143, USA.

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Rosemary J. Akhurst

2Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California at San Francisco, San Francisco, CA 94143, USA.

4Helen Diller Family Comprehensive Cancer Center, University of California at San Francisco, San Francisco, CA 94143, USA.

6Department of Anatomy, University of California at San Francisco, San Francisco, CA 94143, USA.

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Kohei Miyazono

3Department of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.

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Rik Derynck

1Department of Cell and Tissue Biology, University of California at San Francisco, San Francisco, CA 94143, USA.

2Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California at San Francisco, San Francisco, CA 94143, USA.

4Helen Diller Family Comprehensive Cancer Center, University of California at San Francisco, San Francisco, CA 94143, USA.

6Department of Anatomy, University of California at San Francisco, San Francisco, CA 94143, USA.

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For correspondence: rik.derynck@ucsf.edu

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vol. 12 no. 570

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https://doi.org/10.1126/scisignal.aau8544

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Received July 21, 2018
Accepted January 28, 2019
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Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works http://www.sciencemag.org/about/science-licenses-journal-article-reuseThis is an article distributed under the terms of the Science Journals Default License.

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Chronic TGF-β exposure drives stabilized EMT, tumor stemness, and cancer drug resistance with vulnerability to bitopic mTOR inhibition

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