Aldo-keto reductase 1C1 induced by interleukin-1β mediates the invasive potential and drug resistance of metastatic bladder cancer cells.
Aldo-keto reductase 1C1 induced by interleukin-1β mediates the invasive potential and drug resistance of metastatic bladder cancer cells.
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DOI：
10.1038/srep34625
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发表时间：
2016-10-04
影响因子：
4.6
通讯作者：
Tanaka S
中科院分区：
文献类型：
--
作者：
Matsumoto R;Tsuda M;Yoshida K;Tanino M;Kimura T;Nishihara H;Abe T;Shinohara N;Nonomura K;Tanaka S
在膀胱癌的治疗中，确定肿瘤侵袭、转移和耐药的分子机制对于提高患者的长期生存率是迫切的。醛酮还原酶1C 1（aldo-keto reductase 1C 1，AKR 1C 1）是一种重要的代谢酶，在肿瘤的侵袭、转移和化疗耐药中起重要作用。在人膀胱癌细胞系UM-UC-3的原位异种移植模型中，从肝、肺和骨中的肿瘤建立转移性亚系。这些细胞具有升高水平的EMT相关标志物，如Snail、Slug或CD 44，并表现出增强的侵袭。通过微阵列分析，发现AKR 1C 1在转移性病变中上调，这在转移性人膀胱癌标本中得到验证。AKR 1C 1敲低导致的侵袭性降低表明AKR 1C 1在癌症侵袭中的新作用，这可能是由于Rac 1，Src或Akt的调节。发现一种炎性细胞因子白细胞介素-1 β可增加膀胱癌细胞系中的AKR 1C 1。一种特殊的非甾体抗炎药氟芬那酸拮抗AKR 1C 1，降低了转移性亚系的顺铂耐药性和侵袭潜力。这些数据揭示了AKR 1C 1在调节转移和耐药性方面的关键作用;因此，AKR 1C 1应该是浸润性膀胱癌治疗中的有效分子靶点。
In treating bladder cancer, determining the molecular mechanisms of tumor invasion, metastasis, and drug resistance are urgent to improving long-term patient survival. One of the metabolic enzymes, aldo-keto reductase 1C1 (AKR1C1), plays an essential role in cancer invasion/metastasis and chemoresistance. In orthotopic xenograft models of a human bladder cancer cell line, UM-UC-3, metastatic sublines were established from tumors in the liver, lung, and bone. These cells possessed elevated levels of EMT-associated markers, such as Snail, Slug, or CD44, and exhibited enhanced invasion. By microarray analysis, AKR1C1 was found to be up-regulated in metastatic lesions, which was verified in metastatic human bladder cancer specimens. Decreased invasion caused by AKR1C1 knockdown suggests a novel role of AKR1C1 in cancer invasion, which is probably due to the regulation of Rac1, Src, or Akt. An inflammatory cytokine, interleukin-1β, was found to increase AKR1C1 in bladder cancer cell lines. One particular non-steroidal anti-inflammatory drug, flufenamic acid, antagonized AKR1C1 and decreased the cisplatin-resistance and invasion potential of metastatic sublines. These data uncover the crucial role of AKR1C1 in regulating both metastasis and drug resistance; as a result, AKR1C1 should be a potent molecular target in invasive bladder cancer treatment.
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影响因子：
3.7
作者：
Jernberg E;Thysell E;Bovinder Ylitalo E;Rudolfsson S;Crnalic S;Widmark A;Bergh A;Wikström P
通讯作者：
Wikström P
影响因子：
5.7
作者：
Matsumoto R;Tsuda M;Wang L;Maishi N;Abe T;Kimura T;Tanino M;Nishihara H;Hida K;Ohba Y;Shinohara N;Nonomura K;Tanaka S
通讯作者：
Tanaka S
影响因子：
45.3
作者：
Hussain, Maha H. A.;MacVicar, Gary R.;Smith, David C.
通讯作者：
Smith, David C.
DOI：
10.1073/pnas.1313580111
发表时间：
2014-02-11
影响因子：
11.1
作者：
Morrison, Carl D.;Liu, Pengyuan;Trump, Donald L.
通讯作者：
Trump, Donald L.
影响因子：
5.1
作者：
Penning, Trevor M.
通讯作者：
Penning, Trevor M.