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

被引:6
|
作者
Shibasaki, Yuta [1 ]
Yokobori, Takehiko [2 ]
Sohda, Makoto [1 ]
Shioi, Ikuma [1 ]
Ozawa, Naoya [1 ]
Komine, Chika [1 ]
Suga, Kunihiko [1 ]
Nakazawa, Nobuhiro [1 ]
Osone, Katsuya [1 ]
Shiraishi, Takuya [1 ]
Okada, Takuhisa [1 ]
Sano, Akihiko [1 ]
Sakai, Makoto [1 ]
Ogawa, Hiroomi [1 ]
Kaira, Kyoichi [3 ]
Shirabe, Ken [1 ]
Saeki, Hiroshi [1 ]
机构
[1] Gunma Univ, Grad Sch Med, Dept Gen Surg Sci, Maebashi 3718510, Japan
[2] Gunma Univ Initiat Adv Res GIAR, Div Integrated Oncol Res, Maebashi 3718511, Japan
[3] Saitama Univ Hosp, Comprehens Canc Ctr, Int Med Ctr, Dept Resp Med, Hidaka 3501298, Japan
基金
日本学术振兴会;
关键词
L-type amino acid transporter-1; cancer aggressiveness; prognostic marker; chemosensitivity marker; TRANSPORTER; FLUOROURACIL; LEUCOVORIN; LEVAMISOLE; RESISTANCE; THERAPY; ASCT2;
D O I
10.3390/ijms24032604
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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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页数:13
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