1. Department of Colorectal Surgery, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, China.
2. College of Clinical Medicine, Ningxia Medical University, Yinchuan, Ningxia 750004, China.
3. Department of Orthopedics, Shangluo International Medical Center Hospital, Shangluo, Shanxi 726000, China.
4. Department of Occupational and Environmental Health, Public Health and Management School, Ningxia Medical University, Yinchuan, Ningxia 750004, China.
5. Department of Gynaecology, Jingzhou Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Jingzhou, Hubei 434000, China.
6. Department of Gastroenterology, Hospital of Chengdu University of Traditional Chinese Medicine, Sichuan 610072, China.
7. Department of Clinical Oncology, Queen Elizabeth Hospital, Kowloon, Hong Kong.
8. Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in the Western, and College of Life Science, Ningxia University, Yinchuan, Ningxia 750021, China.
Colorectal cancer (CRC) is the second leading cause of death globally. Integrin α1 (ITGA1) belongs to integrin family and involves in regulating cell adhesion, invasion, proliferation and tumorigenicity, its expression is up-regulated in various cancers, including CRC. However, the molecular understanding and clinical relevance of ITGA1 in the development and progression of CRC remain unclear. In the present study, we detected ITGA1 in 50 CRC tissues and adjacent non-cancerous tissues, sera from 100 CRC patients and 50 healthy subjects, and four CRC cell lines using immunohistochemistry staining, enzyme-linked immunosorbent assay and Western blotting. We found that the ITGA1 protein was significantly higher in human CRC tissues and cell lines than both paired non-tumor tissues and normal cells, respectively. In addition, the serum concentration of ITGA1 was also higher in CRC patients compared to the healthy subjects (p<0.01) and was significantly associated with metastatic TNM stages (p<0.0001) and circulating carbohydrate antigen 199 (CA199) (p<0.022). Furthermore, down-regulation of ITGA1 with transfecting LV-shITGA1 inhibited the progressive capacity of cell migration and invasion in CRC SW480 cell line and the tumorgenicity in nude mice. In functional studies, ITGA1 knockdown also inhibited Ras/ERK signaling pathway by decreasing the expression of Ras, p-Erk1/2 and c-Myc in SW480. Contrastly, when evelated expression of ITGA1 in NCM460 coincided with the increased expression of Ras, p-Erk1/2 and c-Myc. Taken together, our findings suggest that ITGA1 is an oncogene with a capability to promote CRC cell migration, invasion and tumorigenicity by activating the Ras/Erk signaling, implying that it may be a novel target for the diagnosis and treatment of CRC, and warrants further investigation.
Keywords: Integrin α1 (ITGA1), colorectal cancer, progression, tumorigenicity