title: Novel role of Sarco/endoplasmic reticulum calcium ATPase 2 in development of colorectal cancer and its regulation by F36, a curcumin analog.
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-Apc(Min/)JNju mice. Besides, SERCA2 expression was also increased in undifferentiated HT-29 cells as compared with that in differentiated HT-29gal 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.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22, Hankou Road, Nanjing 210093, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Fan
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22, Hankou Road, Nanjing 210093, China.
authors.forename: Ang
authors.initials: A
authors.lastname: Li
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22, Hankou Road, Nanjing 210093, China.
authors.forename: Wanshuai
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Clinical Oncology, The First Affiliated Hospital of Nanjing Medical University, 300, Guangzhou Road, Nanjing 210029, China.
authors.forename: Peifen
authors.initials: P
authors.lastname: Cai
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22, Hankou Road, Nanjing 210093, China.
authors.forename: Baofang
authors.initials: B
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22, Hankou Road, Nanjing 210093, China.
authors.forename: Minxia
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Clinical Oncology, The First Affiliated Hospital of Nanjing Medical University, 300, Guangzhou Road, Nanjing 210029, China.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Department of Clinical Oncology, The First Affiliated Hospital of Nanjing Medical University, 300, Guangzhou Road, Nanjing 210029, China.
authors.forename: Yongqian
authors.initials: Y
authors.lastname: Shu
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22, Hankou Road, Nanjing 210093, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22, Hankou Road, Nanjing 210093, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Shen
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22, Hankou Road, Nanjing 210093, China.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22, Hankou Road, Nanjing 210093, China; Department of Pharmacology, Nanjing Medical University, 140, Hanzhong Road, Nanjing 210029, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22, Hankou Road, Nanjing 210093, China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China. Electronic address: xudongwu@nju.edu.cn.
authors.forename: Xudong
authors.initials: X
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22, Hankou Road, Nanjing 210093, China. Electronic address: molpharm@163.com.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xu
mesh_terms: D000818:Animals; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D003474:Curcumin / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D019073:HT29 Cells; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000502:physiology*
chemical_list: D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; C506947:Atp2a2 protein, mouse; D003474:Curcumin
keywords: Colorectal cancer; Differentiation; Proliferation; SERCA2; Tumorigenesis