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TnIK Is a Therapeutic Target in Lung Squamous Cell Carcinoma and Regulates FAK Activation through Merlin

  1. Author:
    Torres-Ayuso,Pedro
    An, Elvira
    Nyswaner,Katherine
    Bensen,Ryan
    Ritt,Daniel
    Specht,Suzanne
    Das,Sudipto
    Andresson,Thorkell
    Cachau,Raul
    Liang, Roger J.
    Ries,Amy
    Robinson,Christina
    Difilippantonio,Simone
    Gouker,Brad
    Gouker,Brad
    Karim,Baktiar
    Miller, Chad J.
    Turk, Benjamin E.
    Morrison,Deborah
    Brognard,John

  2. Author Address

    NCI, Lab Cell & Dev Signaling, Ctr Canc Res, Frederick, MD 21702 USA.Frederick Natl Lab Canc Res, Prot Characterizat Lab, Leidos Biomed Res, Frederick, MD USA.Frederick Natl Lab Canc Res, Adv Biomed Computat Sci, Biomed Informat & Data Sci, Frederick, MD USA.Frederick Natl Lab Canc Res, Lab Anim Sci Program, Leidos Biomed Res, Frederick, MD USA.Frederick Natl Lab Canc Res, Mol Histopathol Lab, Leidos Biomed Res, Frederick, MD USA.Yale Sch Med, Dept Pharmacol, New Haven, CT USA.Univ Washington, Inst Prot Design, Seattle, WA 98195 USA.
    1. Year: 2021
    2. Date: Jun
    3. Epub Date: 2021 Jan 25
  2. Journal: Cancer Discovery
  3. AMER ASSOC CANCER RESEARCH,
    1. 11
    2. 6
    3. Pages: 1411-1423
  5. Type of Article: Article
  6. ISSN: 2159-8274
  1. Abstract:

    Lung squamous cell carcinoma (LSCC) is the second most prevalent type of lung cancer. Despite extensive genomic characterization, no targeted therapies are approved for the treatment of LSCC. Distal amplification of the 3q chromosome is the most frequent genomic alteration in LSCC, and there is an urgent need to identify efficacious druggable targets within this amplicon. We identify the protein kinase TNIK as a therapeutic target in LSCC. TNIK is amplified in approximately 50% of LSCC cases. TNIK genetic depletion or pharmacologic inhibition reduces the growth of LSCC cells in vitro and in vivo. In addition, TNIK inhibition showed antitumor activity and increased apoptosis in established LSCC patient-derived xenografts. Mechanistically, we identified the tumor suppressor Merlin/NF2 as a novel TNIK substrate and showed that TNIK and Merlin are required for the activation of focal adhesion kinase. In conclusion, our data identify targeting TNIK as a potential therapeutic strategy in LSCC.

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External Sources

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  2. DOI: 10.1158/2159-8290.CD-20-0797
  3. PMID: 33495197
  4. View record in Web of Science®
  5. WOS: 000659290300027

Library Notes

  1. Fiscal Year: FY2020-2021
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