Novel role of Sarco/endoplasmic reticulum calcium ATPase 2 in development of colorectal cancer and its regulation by F36, a curcumin analog |
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| Institution: | 1. State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22, Hankou Road, Nanjing 210093, China;2. Department of Clinical Oncology, The First Affiliated Hospital of Nanjing Medical University, 300, Guangzhou Road, Nanjing 210029, China;3. Department of Pharmacology, Nanjing Medical University, 140, Hanzhong Road, Nanjing 210029, China;4. State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China;1. Zoology Department, Faculty of Science, Assiut University, 71516 Assiut, Egypt;2. Laboratory of Immunology & Molecular Physiology, Zoology Department, Faculty of Science, Assiut University, 71516 Assiut, Egypt;3. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ataturk University, Erzurum, Turkey;4. Department of Biochemistry, Faculty of Medicine, Assiut University, 71526 Assiut, Egypt;5. Radiation Biology Department, National Centre for Radiation Research and Technology (NCRRT), Cairo, Egypt;6. Department of Physiology, Faculty of Medicine, Ataturk University, Erzurum, Turkey;7. Department of Chemistry, Faculty of Science, Assiut University, Assiut 71516, Egypt;1. Department of Biochemistry, National Defense Medical Center, 161, Section 6, Min-Chuan East Road, Taipei, Taiwan, ROC;2. Department of Orthopaedics, Chi Mei Medical Center, Tainan, Taiwan, ROC;3. Department of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan, ROC;4. Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC;5. Department of Microbiology, Soochow University, Shihlin, Taipei, Taiwan, ROC;1. Department of Chemistry, Acadia University, Wolfville, Nova Scotia B4P 2R6, Canada;2. Department of Environmental Sciences, Faculty of Agriculture, Dalhousie University, Truro, Nova Scotia B2N 5E3, Canada;3. Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium;3. From the Department of Genetics & Department of Pathogen Biology, School of Basic Medical Sciences, Tianjin 300070, China;5. School of Biomedical Engineering, Tianjin Medical University, Tianjin 300070, China;;6. School of Electronic Information Engineering, Tianjin University, Tianjin 300070, China;;4. Department of Hepatic Biliary Pancreatic Surgery, Cancer Hospital Affiliated to Zhengzhou University, Zhenzhou 450003, China; |
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| Abstract: | Sarco/endoplasmic reticulum calcium ATPase (SERCA) enzymes play important roles in several signal transduction pathways that control proliferation, differentiation and apoptosis. Here, we reported that SERCA2 expression was positively correlated with tumor node metastasis (TNM) stages (n = 75, P = 0.0251) and grades (n = 63, P = 0.0146) of patients with colorectal cancer. The animal experiments demonstrated that SERCA2 expression was consistent with PCNA staining of intestinal tissues of male C57BL/6J-ApcMin/JNju mice. Besides, SERCA2 expression was also increased in undifferentiated HT-29 cells as compared with that in differentiated HT-29 gal cells. Moreover, SERCA2 overexpression promoted proliferation and migration of SW480 cells via activating MAPK and AKT signaling pathways, while silence of SERCA2 inhibited the proliferation and migration of SW480 cells. In addition, we identified that a curcumin analog, F36, exhibited more potent inhibitory effect in colorectal cancer cells than curcumin through inhibiting SERCA2 expression. Taken together, our findings indicate that SERCA2 is involved in the malignant progress of colorectal cancer and maybe a therapeutic target for colorectal cancer treatment. Curcumin analog F36 shows enhanced anti-cancer activity in colorectal cancer cells by targeting SERCA2. |
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| Keywords: | SERCA2 Colorectal cancer Differentiation Proliferation Tumorigenesis |
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