Yasuda Kazuyo, Hirohashi Yoshihiko, Kuroda Takafumi, Takaya Akari, Kubo Terufumi, Kanaseki Takayuki, Tsukahara Tomohide, Hasegawa Tadashi, Saito Tsuyoshi, Sato Noriyuki, Torigoe Toshihiko
Department of Pathology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, 060-8556, Japan.
Department of Pathology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, 060-8556, Japan.
Biochem Biophys Res Commun. 2016 Apr 15;472(4):643-7. doi: 10.1016/j.bbrc.2016.03.004. Epub 2016 Mar 9.
Cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) are defined as small subpopulation of cancer cells that are endowed with higher tumor-initiating ability. CSCs/CICs are resistant to standard cancer therapies including chemotherapy and radiotherapy, and they are thus thought to be responsible for cancer recurrence and metastasis. Therefore, elucidation of molecular mechanisms of CSCs/CICs is essential to cure cancer. In this study, we analyzed the gene expression profiles of gynecological CSCs/CICs isolated as aldehyde dehydrogenase high (ALDH(high)) cells, and found that MAPK13, PTTG1IP, CAPN1 and UBQLN2 were preferentially expressed in CSCs/CICs. MAPK13 is expressed in uterine, ovary, stomach, colon, liver and kidney cancer tissues at higher levels compared with adjacent normal tissues. MAPK13 gene knockdown using siRNA reduced the ALDH(high) population and abrogated the tumor-initiating ability. These results indicate that MAPK13 is expressed in gynecological CSCs/CICs and has roles in the maintenance of CSCs/CICs and tumor-initiating ability, and MAPK13 might be a novel molecular target for treatment-resistant CSCs/CICs.
癌症干细胞（CSCs）/癌症起始细胞（CICs）被定义为具有较高肿瘤起始能力的一小部分癌细胞亚群。CSCs/CICs对包括化疗和放疗在内的标准癌症治疗具有抗性，因此被认为是癌症复发和转移的原因。因此，阐明CSCs/CICs的分子机制对于治愈癌症至关重要。在本研究中，我们分析了作为醛脱氢酶高表达（ALDH(high)）细胞分离出的妇科CSCs/CICs的基因表达谱，发现MAPK13、PTTG1IP、CAPN1和UBQLN2在CSCs/CICs中优先表达。与相邻正常组织相比，MAPK13在子宫、卵巢、胃、结肠、肝脏和肾脏癌组织中表达水平更高。使用siRNA敲低MAPK13基因可减少ALDH(high)细胞群并消除肿瘤起始能力。这些结果表明，MAPK13在妇科CSCs/CICs中表达，并在维持CSCs/CICs和肿瘤起始能力方面发挥作用，MAPK13可能是治疗抗性CSCs/CICs的一个新的分子靶点。
