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L-type amino acid transporter 1 is associated with chemoresistance in breast cancer via the promotion of amino acid metabolism.
Sato, Miku; Harada-Shoji, Narumi; Toyohara, Takafumi; Soga, Tomoyoshi; Itoh, Masatoshi; Miyashita, Minoru; Tada, Hiroshi; Amari, Masakazu; Anzai, Naohiko; Furumoto, Shozo; Abe, Takaaki; Suzuki, Takashi; Ishida, Takanori; Sasano, Hironobu.
Afiliação
  • Sato M; Department of Breast and Endocrine Surgical Oncology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan.
  • Harada-Shoji N; Department of Pathology, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan.
  • Toyohara T; Department of Breast and Endocrine Surgical Oncology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan. n.harada@med.tohoku.ac.jp.
  • Soga T; Division of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan.
  • Itoh M; Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata, 997-0035, Japan.
  • Miyashita M; Sendai Medical Imaging Center, 2-1-25 Itsutsubashi, Aoba-ku, Sendai, 980-0022, Japan.
  • Tada H; Department of Breast and Endocrine Surgical Oncology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan.
  • Amari M; Department of Breast and Endocrine Surgical Oncology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan.
  • Anzai N; Department of Breast Surgery, Tohoku Kosai Hospital, 2-3-11 Kokubuncho, Aoba-ku, Sendai, 980-0803, Japan.
  • Furumoto S; Department of Pharmacology, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chiba, 260-0856, Japan.
  • Abe T; Cyclotron and Radioisotope Center, Tohoku University School of Medicine, 6-3 Aramaki-aza-Aoba, Aoba-ku, Sendai, 980-8578, Japan.
  • Suzuki T; Division of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan.
  • Ishida T; Department of Pathology and Histotechonology, Tohoku University Graduate School of Medicine, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan.
  • Sasano H; Department of Breast and Endocrine Surgical Oncology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan.
Sci Rep ; 11(1): 589, 2021 01 12.
Article em En | MEDLINE | ID: mdl-33436954
18F-FDG PET/CT has been used as an indicator of chemotherapy effects, but cancer cells can remain even when no FDG uptake is detected, indicating the importance of exploring other metabolomic pathways. Therefore, we explored the amino acid metabolism, including L-type amino acid transporter-1 (LAT1), in breast cancer tissues and clarified the role of LAT1 in therapeutic resistance and clinical outcomes of patients. We evaluated LAT1 expression before and after neoadjuvant chemotherapy and examined the correlation of glucose uptake using FDG-PET with the pathological response of patients. It revealed that LAT1 levels correlated with proliferation after chemotherapy, and amino acid and glucose metabolism were closely correlated. In addition, LAT1 was considered to be involved in treatment resistance and sensitivity only in luminal type breast cancer. Results of in vitro analyses revealed that LAT1 promoted amino acid uptake, which contributed to energy production by supplying amino acids to the TCA cycle. However, in MCF-7 cells treated with chemotherapeutic agents, oncometabolites and branched-chain amino acids also played a pivotal role in energy production and drug resistance, despite decreased glucose metabolism. In conclusion, LAT1 was involved in drug resistance and could be a novel therapeutic target against chemotherapy resistance in luminal type breast cancer.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Expressão Gênica / Transportador 1 de Aminoácidos Neutros Grandes / Aminoácidos Tipo de estudo: Risk_factors_studies Limite: Aged / Female / Humans / Middle aged Idioma: En Revista: Sci Rep Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Expressão Gênica / Transportador 1 de Aminoácidos Neutros Grandes / Aminoácidos Tipo de estudo: Risk_factors_studies Limite: Aged / Female / Humans / Middle aged Idioma: En Revista: Sci Rep Ano de publicação: 2021 Tipo de documento: Article