Your browser doesn't support javascript.
loading
Clinical potential of SKP2 as diagnostic marker and therapeutic target in small cell lung cancer.
Matsumoto, Naohisa; Tajima, Ken; Takahashi, Fumiyuki; Mitsuishi, Yoichiro; Wirawan, Aditya; Hidayat, Moulid; Winardi, Wira; Wibowo, Adityo; Hayakawa, Daisuke; Izumi, Kenta; Kanamori, Koichiro; Miyashita, Yosuke; Handa, Takafumi; Asao, Tetsuhiko; Ko, Ryo; Shukuya, Takehito; Shimada, Naoko; Takamochi, Kazuya; Hayashi, Takuo; Suzuki, Kenji; Takahashi, Kazuhisa.
Afiliación
  • Matsumoto N; Department of Respiratory Medicine, Juntendo University, Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan; Research Institute for Diseases of Old Ages, Juntendo University, Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan.
  • Tajima K; Department of Respiratory Medicine, Juntendo University, Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan; Research Institute for Diseases of Old Ages, Juntendo University, Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan. Electronic address: tajik
  • Takahashi F; Department of Respiratory Medicine, Juntendo University, Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan; Research Institute for Diseases of Old Ages, Juntendo University, Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan.
  • Mitsuishi Y; Department of Respiratory Medicine, Juntendo University, Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan; Research Institute for Diseases of Old Ages, Juntendo University, Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan.
  • Wirawan A; Department of Respiratory Medicine, Juntendo University, Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan; Research Institute for Diseases of Old Ages, Juntendo University, Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan.
  • Hidayat M; Department of Respiratory Medicine, Juntendo University, Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan; Research Institute for Diseases of Old Ages, Juntendo University, Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan.
  • Winardi W; Department of Respiratory Medicine, Juntendo University, Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan; Research Institute for Diseases of Old Ages, Juntendo University, Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan.
  • Wibowo A; Department of Respiratory Medicine, Juntendo University, Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan; Research Institute for Diseases of Old Ages, Juntendo University, Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan.
  • Hayakawa D; Department of Respiratory Medicine, Juntendo University, Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan; Research Institute for Diseases of Old Ages, Juntendo University, Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan.
  • Izumi K; Department of Respiratory Medicine, Juntendo University, Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan; Research Institute for Diseases of Old Ages, Juntendo University, Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan.
  • Kanamori K; Department of Respiratory Medicine, Juntendo University, Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan; Research Institute for Diseases of Old Ages, Juntendo University, Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan.
  • Miyashita Y; Department of Respiratory Medicine, Juntendo University, Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan; Research Institute for Diseases of Old Ages, Juntendo University, Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan.
  • Handa T; Department of Human Pathology, Juntendo University, Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan.
  • Asao T; Department of Respiratory Medicine, Juntendo University, Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan; Research Institute for Diseases of Old Ages, Juntendo University, Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan.
  • Ko R; Department of Respiratory Medicine, Juntendo University, Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan; Research Institute for Diseases of Old Ages, Juntendo University, Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan.
  • Shukuya T; Department of Respiratory Medicine, Juntendo University, Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan; Research Institute for Diseases of Old Ages, Juntendo University, Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan.
  • Shimada N; Department of Respiratory Medicine, Juntendo University, Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan; Research Institute for Diseases of Old Ages, Juntendo University, Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan.
  • Takamochi K; Department of General Thoracic Surgery, Juntendo University, Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan.
  • Hayashi T; Department of Human Pathology, Juntendo University, Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan.
  • Suzuki K; Department of General Thoracic Surgery, Juntendo University, Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan.
  • Takahashi K; Department of Respiratory Medicine, Juntendo University, Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan; Research Institute for Diseases of Old Ages, Juntendo University, Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan.
Respir Investig ; 62(5): 901-909, 2024 Sep.
Article en En | MEDLINE | ID: mdl-39116798
ABSTRACT

BACKGROUND:

Small cell lung cancer (SCLC) is the most aggressive type of lung cancer. The overall survival has not improved significantly over the last decades because no major therapeutic breakthroughs have been achieved for over 15 years.

METHODS:

We analyzed a genome-wide loss-of-function screening database to identify vulnerabilities in SCLC for the development of urgently needed novel therapies.

RESULTS:

We identified SKP2 (encoding S-phase kinase-associated protein 2) and CKS1B (encoding CDC28 protein kinase regulatory subunit 1B) as the two most essential genes in that order in SCLC. Notably, SKP2 and CKS1B comprise the p27 binding pocket of the E3 ubiquitin ligase SCFSKP2 complex. Immunohistochemistry on tissue microarrays revealed that SKP2 was expressed in >95% of samples at substantially higher levels than that observed for commonly used neuroendocrine markers. As expected, SCLC cell lines were sensitive to SKP2 inhibition. Furthermore, SKP2 or CKS1B knockdown induced apoptosis in RB1 mutant cells, whereas it induced senescence in RB1 wild-type cells.

CONCLUSION:

Although the mechanism underlying SKP2 knockdown-induced growth inhibition differs between RB1-wild-type and -mutant SCLC, SKP2 can be considered a novel therapeutic target for patients with SCLC regardless of the RB1 mutation status. Our findings indicate that SKP2 is a potential novel clinical diagnostic marker and therapeutic target in SCLC.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Biomarcadores de Tumor / Quinasas CDC2-CDC28 / Proteínas Quinasas Asociadas a Fase-S / Carcinoma Pulmonar de Células Pequeñas / Neoplasias Pulmonares Límite: Humans Idioma: En Revista: Respir Investig Año: 2024 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Biomarcadores de Tumor / Quinasas CDC2-CDC28 / Proteínas Quinasas Asociadas a Fase-S / Carcinoma Pulmonar de Células Pequeñas / Neoplasias Pulmonares Límite: Humans Idioma: En Revista: Respir Investig Año: 2024 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Países Bajos