Focal adhesion kinase-YAP signaling axis drives drug-tolerant persister cells and residual disease in lung cancer.

Humans Lung Neoplasms / drug therapy Signal Transduction / drug effects Transcription Factors / metabolism Carcinoma, Non-Small-Cell Lung / drug therapy YAP-Signaling Proteins / metabolism Cell Line, Tumor Animals Drug Resistance, Neoplasm / genetics Adaptor Proteins, Signal Transducing / metabolism Neoplasm, Residual Mice Focal Adhesion Kinase 1 / metabolism ErbB Receptors / metabolism Anaplastic Lymphoma Kinase / metabolism Proto-Oncogene Proteins p21(ras) / genetics Focal Adhesion Protein-Tyrosine Kinases / metabolism Antineoplastic Agents / therapeutic use Xenograft Model Antitumor Assays

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
03 May 2024
Historique:
received: 04 01 2022
accepted: 18 03 2024
medline: 4 5 2024
pubmed: 4 5 2024
entrez: 3 5 2024
Statut: epublish

Résumé

Targeted therapy is effective in many tumor types including lung cancer, the leading cause of cancer mortality. Paradigm defining examples are targeted therapies directed against non-small cell lung cancer (NSCLC) subtypes with oncogenic alterations in EGFR, ALK and KRAS. The success of targeted therapy is limited by drug-tolerant persister cells (DTPs) which withstand and adapt to treatment and comprise the residual disease state that is typical during treatment with clinical targeted therapies. Here, we integrate studies in patient-derived and immunocompetent lung cancer models and clinical specimens obtained from patients on targeted therapy to uncover a focal adhesion kinase (FAK)-YAP signaling axis that promotes residual disease during oncogenic EGFR-, ALK-, and KRAS-targeted therapies. FAK-YAP signaling inhibition combined with the primary targeted therapy suppressed residual drug-tolerant cells and enhanced tumor responses. This study unveils a FAK-YAP signaling module that promotes residual disease in lung cancer and mechanism-based therapeutic strategies to improve tumor response.

Identifiants

DOI: 10.1038/s41467-024-47423-0 PMID: 38702301
pubmed: 38702301
doi: 10.1038/s41467-024-47423-0
pii: 10.1038/s41467-024-47423-0
doi:

Substances chimiques

Transcription Factors 0
YAP1 protein, human 0
YAP-Signaling Proteins 0
Adaptor Proteins, Signal Transducing 0
PTK2 protein, human EC 2.7.10.2
Focal Adhesion Kinase 1 EC 2.7.10.2
ErbB Receptors EC 2.7.10.1
Anaplastic Lymphoma Kinase EC 2.7.10.1
Proto-Oncogene Proteins p21(ras) EC 3.6.5.2
EGFR protein, human EC 2.7.10.1
KRAS protein, human 0
ALK protein, human EC 2.7.10.1
Focal Adhesion Protein-Tyrosine Kinases EC 2.7.10.2
Antineoplastic Agents 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

3741

Informations de copyright

© 2024. The Author(s).

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Auteurs

Franziska Haderk (F)

Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA.
ORCID: 0000-0001-9658-2778

Yu-Ting Chou (YT)

Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA.

Lauren Cech (L)

Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA.
ORCID: 0000-0002-3621-4129

Celia Fernández-Méndez (C)

Instituto de Investigaciones Biomédicas "Alberto Sols", Consejo Superior de Investigaciones Científícas (CSIC) y Universidad Autónoma de Madrid (UAM), Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain.
ORCID: 0000-0001-8593-5507

Johnny Yu (J)

Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.
Department of Biochemistry & Biophysics, University of California, San Francisco, San Francisco, CA, USA.
Department of Urology, University of California, San Francisco, San Francisco, CA, USA.

Victor Olivas (V)

Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA.

Ismail M Meraz (IM)

Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
ORCID: 0000-0001-9109-5196

Dora Barbosa Rabago (D)

Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA.

D Lucas Kerr (DL)

Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
ORCID: 0000-0002-0557-8341

Carlos Gomez (C)

Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.

David V Allegakoen (DV)

Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.

Juan Guan (J)

Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA.

Khyati N Shah (KN)

Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.
Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA.

Kari A Herrington (KA)

Center for Advanced Light Microscopy, University of California, San Francisco, San Francisco, CA, USA.
ORCID: 0000-0003-4925-8072

Oghenekevwe M Gbenedio (OM)

Department of Anatomy, University of California, San Francisco, San Francisco, CA, USA.

Shigeki Nanjo (S)

Division of Medical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan.
ORCID: 0000-0001-8356-9849

Mourad Majidi (M)

Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Whitney Tamaki (W)

Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
ORCID: 0000-0002-1124-628X

Yashar K Pourmoghadam (YK)

Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.

Julia K Rotow (JK)

Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.

Caroline E McCoach (CE)

Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.

Jonathan W Riess (JW)

University of California Davis Comprehensive Cancer Center, Sacramento, CA, USA.
ORCID: 0000-0001-7370-7304

J Silvio Gutkind (JS)

Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA.
ORCID: 0000-0002-5150-4482

Tracy T Tang (TT)

Vivace Therapeutics, Inc., 1500 Fashion Island Blvd., Suite 102, San Mateo, CA, USA.

Leonard Post (L)

Vivace Therapeutics, Inc., 1500 Fashion Island Blvd., Suite 102, San Mateo, CA, USA.

Bo Huang (B)

Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA.
Department of Biochemistry & Biophysics, University of California, San Francisco, San Francisco, CA, USA.
Chan Zuckerberg Biohub, San Francisco, CA, USA.
ORCID: 0000-0003-1704-4141

Pilar Santisteban (P)

Instituto de Investigaciones Biomédicas "Alberto Sols", Consejo Superior de Investigaciones Científícas (CSIC) y Universidad Autónoma de Madrid (UAM), Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain.
ORCID: 0000-0002-2758-796X

Hani Goodarzi (H)

Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.
Department of Biochemistry & Biophysics, University of California, San Francisco, San Francisco, CA, USA.
Department of Urology, University of California, San Francisco, San Francisco, CA, USA.
ORCID: 0000-0002-9648-8949

Sourav Bandyopadhyay (S)

Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.
Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA.
ORCID: 0000-0003-3120-923X

Calvin J Kuo (CJ)

Department of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, CA, USA.
ORCID: 0000-0002-7427-5985

Jeroen P Roose (JP)

Department of Anatomy, University of California, San Francisco, San Francisco, CA, USA.
ORCID: 0000-0003-4746-2811

Wei Wu (W)

Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
ORCID: 0000-0002-6556-067X

Collin M Blakely (CM)

Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.
ORCID: 0000-0001-8134-3651

Jack A Roth (JA)

Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
ORCID: 0000-0002-8955-1313

Trever G Bivona (TG)

Department of Medicine, University of California, San Francisco, San Francisco, CA, USA. trever.bivona@ucsf.edu.
Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA. trever.bivona@ucsf.edu.
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA. trever.bivona@ucsf.edu.
ORCID: 0000-0001-5734-4128

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Focal adhesion kinase-YAP signaling axis...
questionsmedicales.fr › Maladies de l'appareil respiratoire › Tumeurs de l'appareil respiratoire › Tumeurs du poumon › Focal adhesion kinase-YAP signaling axis...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › Focal adhesion kinase-YAP signaling axis...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Focal adhesion kinase-YAP signaling axis...
questionsmedicales.fr › Maladies de l'appareil respiratoire › Tumeurs de l'appareil respiratoire › Tumeurs du poumon › Tumeurs des bronches › Carcinome bronchogénique › Carcinome pulmonaire non à petites cellules › Focal adhesion kinase-YAP signaling axis...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protéines adaptatrices de la transduction du signal › Protéines de signalisation YAP › Focal adhesion kinase-YAP signaling axis...
questionsmedicales.fr › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Lignée cellulaire tumorale › Focal adhesion kinase-YAP signaling axis...
questionsmedicales.fr › Eucaryotes › Animaux › Focal adhesion kinase-YAP signaling axis...
questionsmedicales.fr › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Phénomènes pharmacologiques › Résistance aux substances › Résistance aux médicaments antinéoplasiques › Focal adhesion kinase-YAP signaling axis...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protéines adaptatrices de la transduction du signal › Focal adhesion kinase-YAP signaling axis...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Processus néoplasiques › Maladie résiduelle › Focal adhesion kinase-YAP signaling axis...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Focal adhesion kinase-YAP signaling axis...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Phosphoprotéines › Focal adhesion kinase 1 › Focal adhesion kinase-YAP signaling axis...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs peptidiques › Récepteur facteur croissance › Récepteurs ErbB › Focal adhesion kinase-YAP signaling axis...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs à activité tyrosine kinase › Kinase du lymphome anaplasique › Focal adhesion kinase-YAP signaling axis...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines tumorales › Protéines oncogènes › Protéines proto-oncogènes › Protéines proto-oncogènes p21(ras) › Focal adhesion kinase-YAP signaling axis...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protein-tyrosine kinases › Focal adhesion protein-tyrosine kinases › Focal adhesion kinase-YAP signaling axis...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Antinéoplasiques › Focal adhesion kinase-YAP signaling axis...
questionsmedicales.fr › Techniques d'investigation › Transplantation tumorale › Tests d'activité antitumorale sur modèle de xénogreffe › Focal adhesion kinase-YAP signaling axis...