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Article

Association of High LAT1 Expression with Poor Prognosis and Recurrence in Colorectal Cancer Patients Treated with Oxaliplatin-Based Adjuvant Chemotherapy

by
Yuta Shibasaki
1,
Takehiko Yokobori
2,*,
Makoto Sohda
1,*,
Ikuma Shioi
1,
Naoya Ozawa
1,
Chika Komine
1,
Kunihiko Suga
1,
Nobuhiro Nakazawa
1,
Katsuya Osone
1,
Takuya Shiraishi
1,
Takuhisa Okada
1,
Akihiko Sano
1,
Makoto Sakai
1,
Hiroomi Ogawa
1,
Kyoichi Kaira
3,
Ken Shirabe
1 and
Hiroshi Saeki
1
1
Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi 371-8510, Japan
2
Division of Integrated Oncology Research, Gunma University, Initiative for Advanced Research (GIAR), Maebashi 371-8511, Japan
3
Department of Respiratory Medicine, Comprehensive Cancer Center, International Medical Center, Saitama University Hospital, Hidaka 350-1298, Japan
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2023, 24(3), 2604; https://doi.org/10.3390/ijms24032604
Submission received: 22 November 2022 / Revised: 13 January 2023 / Accepted: 26 January 2023 / Published: 30 January 2023
(This article belongs to the Special Issue Advanced Molecular Research on Gastrointestinal Diseases)
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Abstract

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.
Keywords: L-type amino acid transporter-1; cancer aggressiveness; prognostic marker; chemosensitivity marker L-type amino acid transporter-1; cancer aggressiveness; prognostic marker; chemosensitivity marker

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MDPI and ACS Style

Shibasaki, Y.; Yokobori, T.; Sohda, M.; Shioi, I.; Ozawa, N.; Komine, C.; Suga, K.; Nakazawa, N.; Osone, K.; Shiraishi, T.; et al. Association of High LAT1 Expression with Poor Prognosis and Recurrence in Colorectal Cancer Patients Treated with Oxaliplatin-Based Adjuvant Chemotherapy. Int. J. Mol. Sci. 2023, 24, 2604. https://doi.org/10.3390/ijms24032604

AMA Style

Shibasaki Y, Yokobori T, Sohda M, Shioi I, Ozawa N, Komine C, Suga K, Nakazawa N, Osone K, Shiraishi T, et al. Association of High LAT1 Expression with Poor Prognosis and Recurrence in Colorectal Cancer Patients Treated with Oxaliplatin-Based Adjuvant Chemotherapy. International Journal of Molecular Sciences. 2023; 24(3):2604. https://doi.org/10.3390/ijms24032604

Chicago/Turabian Style

Shibasaki, Yuta, Takehiko Yokobori, Makoto Sohda, Ikuma Shioi, Naoya Ozawa, Chika Komine, Kunihiko Suga, Nobuhiro Nakazawa, Katsuya Osone, Takuya Shiraishi, and et al. 2023. "Association of High LAT1 Expression with Poor Prognosis and Recurrence in Colorectal Cancer Patients Treated with Oxaliplatin-Based Adjuvant Chemotherapy" International Journal of Molecular Sciences 24, no. 3: 2604. https://doi.org/10.3390/ijms24032604

APA Style

Shibasaki, Y., Yokobori, T., Sohda, M., Shioi, I., Ozawa, N., Komine, C., Suga, K., Nakazawa, N., Osone, K., Shiraishi, T., Okada, T., Sano, A., Sakai, M., Ogawa, H., Kaira, K., Shirabe, K., & Saeki, H. (2023). Association of High LAT1 Expression with Poor Prognosis and Recurrence in Colorectal Cancer Patients Treated with Oxaliplatin-Based Adjuvant Chemotherapy. International Journal of Molecular Sciences, 24(3), 2604. https://doi.org/10.3390/ijms24032604

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