Targeting the facilitative glucose transporter GLUT1 inhibits the self-renewal and tumor-initiating capacity of cancer stem cells.
Targeting the facilitative glucose transporter GLUT1 inhibits the self-renewal and tumor-initiating capacity of cancer stem cells.
复制标题
DOI：
10.18632/oncotarget.2892
复制
发表时间：
2015-01-20
期刊：
影响因子：
--
通讯作者：
Kitanaka C
中科院分区：
文献类型：
--
作者：
Shibuya K;Okada M;Suzuki S;Seino M;Seino S;Takeda H;Kitanaka C
葡萄糖代谢增加现在被认为是癌症的一个新标志。最近的研究表明，癌症干细胞 (CSC) 中的葡萄糖代谢更加活跃，这是一种罕见的癌细胞群，具有自我更新和引发肿瘤的能力，并且 CSC 的生存/生长依赖于糖酵解。然而，葡萄糖代谢在控制其自我更新和肿瘤引发能力本身中的作用仍然不清楚。此外，对于参与葡萄糖代谢的众多分子中的哪一个适合作为控制 CSC 的靶标，目前仍不清楚。在这里，我们证明了促进性葡萄糖转运蛋白 GLUT1 对于维持胰腺、卵巢和胶质母细胞瘤 CSC 至关重要。值得注意的是，我们发现 WZB117（一种特异性 GLUT1 抑制剂）可以抑制 CSC 的自我更新和肿瘤启动能力，而不损害其体外增殖潜力。在体内，全身施用 WZB117 可抑制 CSC 植入后肿瘤的发生，而不会在宿主动物中引起明显的不良事件。我们的研究结果表明，GLUT1 依赖性葡萄糖代谢不仅在 CSC 的生长和存活中发挥着关键作用，而且在其干性的维持中也发挥着关键作用，并表明 GLUT1 作为 CSC 导向的癌症治疗的一个有前景的靶点。
Increased glucose metabolism is now recognized as an emerging hallmark of cancer. Recent studies have shown that glucose metabolism is even more active in cancer stem cells (CSCs), a rare population of cancer cells with the capacity to self-renew and initiate tumors, and that CSCs are dependent on glycolysis for their survival/growth. However, the role of glucose metabolism in the control of their self-renewal and tumor-initiating capacity per se still remains obscure. Moreover, much remains unknown as to which of the numerous molecules involved in the glucose metabolism is suitable as a target to control CSCs. Here we demonstrate that the facilitative glucose transporter GLUT1 is essential for the maintenance of pancreatic, ovarian, and glioblastoma CSCs. Notably, we found that WZB117, a specific GLUT1 inhibitor, could inhibit the self-renewal and tumor-initiating capacity of the CSCs without compromising their proliferative potential in vitro. In vivo, systemic WZB117 administration inhibited tumor initiation after implantation of CSCs without causing significant adverse events in host animals. Our findings indicate GLUT1-dependent glucose metabolism has a pivotal role not only in the growth and survival of CSCs but also in the maintenance of their stemness and suggest GLUT1 as a promising target for CSC-directed cancer therapy.
登录
查看更多内容
影响因子：
11.2
作者：
Furuta, Eiji;Okuda, Hiroshi;Kobayashi, Aya;Watabe, Kounosuke
通讯作者：
Watabe, Kounosuke
影响因子：
4.1
作者：
Pereira da Silva, Ana Paula;El-Bacha, Tatiana;Galina, Antonio
通讯作者：
Galina, Antonio
影响因子：
--
作者：
Bao, Bin;Ahmad, Aamir;Azmi, Asfar S;Ali, Shadan;Sarkar, Fazlul H
通讯作者：
Sarkar, Fazlul H
影响因子：
25
作者：
Flavahan, William A.;Wu, Qiulian;Hitomi, Masahiro;Rahim, Nasiha;Kim, Youngmi;Sloan, Andrew E.;Weil, Robert J.;Nakano, Ichiro;Sarkaria, Jann N.;Stringer, Brett W.;Day, Bryan W.;Li, Meizhang;Lathia, Justin D.;Rich, Jeremy N.;Hjelmeland, Anita B.
通讯作者：
Hjelmeland, Anita B.
影响因子：
--
作者：
Okada M;Shibuya K;Sato A;Seino S;Suzuki S;Seino M;Kitanaka C
通讯作者：
Kitanaka C