机构：[1]Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, China), the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.[2]Department of Abdominal Oncology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.[3]Department of Medical Oncology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Chloride channel accessory 1 (CLCA1) belongs to the calcium-sensitive chloride conductance protein family, which is mainly expressed in the colon, small intestine and appendix. This study was conducted to investigate the functions and mechanisms of CLCA1 in colorectal cancer (CRC).
The CLCA1 protein expression level in CRC patients was evaluated by enzyme-linked immunosorbent assay (ELISA), immunohistochemistry (IHC), and western blotting analysis. Using CRISPR/Cas9 technology, CLCA1-upregulated (CLCA1-ACT) and CLCA1-knockout cells (CLCA1-KO), as well as their respective negative controls (CLCA1-ACT-NC and CLCA1-KO-NC), were constructed from the SW620 cell line. Cell growth and metastatic ability were assessed both in vitro and in vivo. The association of CLCA1 with epithelial-mesenchymal transition (EMT) and other signaling pathways was determined by western blotting assays.
The expression level of CLCA1 in CRC tissues was significantly decreased compared with that in adjacent normal tissue (P< 0.05). Meanwhile, the serum concentration of CLCA1 in CRC patients was also significantly lower when compared with that of healthy controls (1.48 ± 1.06 ng/mL vs 1.06 ± 0.73 ng/mL, P = 0.0018). In addition, CLCA1 serum concentration and mRNA expression level in CRC tissues were inversely correlated with CRC metastasis and tumor stage. Upregulated CLCA1 suppressed CRC growth and metastasis in vitro and in vivo, whereas inhibition of CLCA1 led to the opposite results. Increased expression levels of CLCA1 could repress Wnt signaling and the EMT process in CRC cells.
Our findings suggest that increased expression levels of CLCA1 can suppress CRC aggressiveness. CLCA1 functions as a tumor suppressor possibly via inhibition of the Wnt/beta-catenin signaling pathway and the EMT process.
基金：
Key Projects in the National Science & Technology Pillar Program during the Twelfth Five-year Plan Period [2014BAI09B07]; National High Technology Research and Development Program of ChinaNational High Technology Research and Development Program of China [2012AA02A506]
语种：
外文
WOS：
PubmedID：
中科院(CAS)分区：
出版当年[2017]版：
大类|2 区生物
小类|3 区细胞生物学
最新[2023]版：
大类|2 区生物学
小类|2 区细胞生物学
第一作者：
第一作者机构：[1]Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, China), the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.[2]Department of Abdominal Oncology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
共同第一作者：
通讯作者：
通讯机构：[1]Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, China), the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
推荐引用方式(GB/T 7714)：
Li Xiaofen,Hu Wangxiong,Zhou Jiaojiao,et al.CLCA1 suppresses colorectal cancer aggressiveness via inhibition of the Wnt/beta-catenin signaling pathway.[J].CELL COMMUNICATION AND SIGNALING.2017,15(1):38.doi:10.1186/s12964-017-0192-z.
APA：
Li Xiaofen,Hu Wangxiong,Zhou Jiaojiao,Huang Yanqin,Peng Jiaping...&Zheng Shu.(2017).CLCA1 suppresses colorectal cancer aggressiveness via inhibition of the Wnt/beta-catenin signaling pathway..CELL COMMUNICATION AND SIGNALING,15,(1)
MLA：
Li Xiaofen,et al."CLCA1 suppresses colorectal cancer aggressiveness via inhibition of the Wnt/beta-catenin signaling pathway.".CELL COMMUNICATION AND SIGNALING 15..1(2017):38
