Kikuchi Daiki, Saito Motonobu, Saito Katsuharu, Watanabe Yohei, Matsumoto Yoshiko, Kanke Yasuyuki, Onozawa Hisashi, Hayase Suguru, Sakamoto Wataru, Ishigame Teruhide, Momma Tomoyuki, Ohki Shinji, Takenoshita Seiichi
Department of Organ Regulatory Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan.
Oncol Lett. 2018 Feb;15(2):2065-2072. doi: 10.3892/ol.2017.7559. Epub 2017 Dec 8.
Solute carrier (SLC) drug transporters exchange various molecules without energy from adenosine triphosphate hydrolysis, indicating an association with anticancer drug resistance. However, the expression and role of SLC transporters in malignant tumors has not yet been fully elucidated. Therefore, in the current study, the expression of SLC37A family genes was evaluated in patients with colorectal cancer (CRC), and it was revealed that SLC family 37 member 1 (SLC37A1) expression was significantly increased in tumorous tissues compared with that in non-tumorous tissues. The cases with upregulated expression of SLC37A1 by immunohistochemical staining were significantly associated with positive venous invasion and liver metastasis. Furthermore, upregulated SLC37A1 expression was associated with poor overall survival time in the present cohort. These results indicated that SLC37A1 is involved in the hematogenous metastasis of CRC. To investigate whether SLC37A1 is associated with hematogenous metastasis and glycolipid metabolism, SLC37A1 was knocked down in colon cancer cells, and the expression of sialyl Lewis A and sialyl Lewis X was observed to be decreased. In summary, upregulation of SLC37A1 was observed in patients with CRC, and was associated with poor patient outcomes and survival. To the best of our knowledge, the present study is the first to propose a key role of SLC37A1 in CRC, and additional studies are warranted to reveal the functional role of SLC37A1 in CRC development.
溶质载体（SLC）药物转运蛋白可在不依赖三磷酸腺苷水解产生能量的情况下交换各种分子，这表明其与抗癌药物耐药性有关。然而，SLC转运蛋白在恶性肿瘤中的表达及作用尚未完全阐明。因此，在本研究中，我们评估了结直肠癌（CRC）患者中SLC37A家族基因的表达，结果显示，与非肿瘤组织相比，肿瘤组织中溶质载体家族37成员1（SLC37A1）的表达显著增加。免疫组化染色显示SLC37A1表达上调的病例与静脉侵犯阳性和肝转移显著相关。此外，在本队列中，SLC37A1表达上调与总生存时间较短有关。这些结果表明，SLC37A1参与了CRC的血行转移。为了研究SLC37A1是否与血行转移及糖脂代谢相关，我们在结肠癌细胞中敲低了SLC37A1，发现唾液酸化路易斯A和唾液酸化路易斯X的表达降低。总之，我们观察到CRC患者中SLC37A1表达上调，且与患者不良预后及生存率相关。据我们所知，本研究首次提出SLC37A1在CRC中起关键作用，有必要开展更多研究以揭示SLC37A1在CRC发生发展中的功能作用。
