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Association of High LAT1 Expression with Poor Prognosis and Recurrence in Colorectal Cancer Patients Treated with Oxaliplatin-Based Adjuvant Chemotherapy.
Shibasaki, Yuta; Yokobori, Takehiko; Sohda, Makoto; Shioi, Ikuma; Ozawa, Naoya; Komine, Chika; Suga, Kunihiko; Nakazawa, Nobuhiro; Osone, Katsuya; Shiraishi, Takuya; Okada, Takuhisa; Sano, Akihiko; Sakai, Makoto; Ogawa, Hiroomi; Kaira, Kyoichi; Shirabe, Ken; Saeki, Hiroshi.
Afiliación
  • Shibasaki Y; Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi 371-8510, Japan.
  • Yokobori T; Division of Integrated Oncology Research, Gunma University, Initiative for Advanced Research (GIAR), Maebashi 371-8511, Japan.
  • Sohda M; Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi 371-8510, Japan.
  • Shioi I; Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi 371-8510, Japan.
  • Ozawa N; Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi 371-8510, Japan.
  • Komine C; Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi 371-8510, Japan.
  • Suga K; Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi 371-8510, Japan.
  • Nakazawa N; Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi 371-8510, Japan.
  • Osone K; Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi 371-8510, Japan.
  • Shiraishi T; Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi 371-8510, Japan.
  • Okada T; Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi 371-8510, Japan.
  • Sano A; Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi 371-8510, Japan.
  • Sakai M; Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi 371-8510, Japan.
  • Ogawa H; Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi 371-8510, Japan.
  • Kaira K; Department of Respiratory Medicine, Comprehensive Cancer Center, International Medical Center, Saitama University Hospital, Hidaka 350-1298, Japan.
  • Shirabe K; Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi 371-8510, Japan.
  • Saeki H; Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi 371-8510, Japan.
Int J Mol Sci ; 24(3)2023 Jan 30.
Article en En | MEDLINE | ID: mdl-36768934
The mammalian target of rapamycin (mTOR) is often activated in several cancers. We focused on two mTOR regulatory mechanisms: oxaliplatin-induced mTOR signaling and L-type amino acid transporter 1 (LAT1)-induced mTOR activation. High LAT1 expression in several cancers is associated with mTOR activation and resistance to chemotherapy. However, the significance of LAT1 has not yet been elucidated in colorectal cancer (CRC) patients treated with post-operative adjuvant chemotherapy. Immunohistochemistry was conducted to examine the significance of membrane LAT1 expression in 98 CRC patients who received adjuvant chemotherapy, including oxaliplatin. In vitro analysis was performed using CRC cell lines to determine the effects of LAT1 suppression on proliferation, oxaliplatin sensitivity, and mTOR signaling. LAT1 expression was associated with cancer aggressiveness and poor prognosis in 98 CRC patients treated with adjuvant chemotherapy. We found that positive LAT1 expression correlated with shorter survival in 43 patients treated with the capecitabine-plus-oxaliplatin (CAPOX) regimen. LAT1 suppression in CRC cells inhibited the proliferation potency and oxaliplatin-induced activation of mTOR signaling, and improved oxaliplatin sensitivity. LAT1 evaluation before adjuvant treatment may therefore be a sensitive marker for oxaliplatin-based regimens. Moreover, LAT1 may be a promising target for patients with refractory CRC.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Colorrectales Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Int J Mol Sci Año: 2023 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Suiza

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Colorrectales Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Int J Mol Sci Año: 2023 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Suiza