Peran FBXW7 pada Stem Cell Normal dan Cancer Stem Cell
DOI:
https://doi.org/10.29303/jku.v5i2.195Keywords:
peran FBXW7, stem cell normal, cancer stem cell, Pathway signal FBXW7Abstract
F-box and WD40 repeat domain-containing 7 (FBXW7) adalah protein F-box yang merupakan komponen sistem ubiquitin proteasome yang berhubungan dengan beberapa protein onkogenik penting seperti Notch, c-Myc, cyclin E and c-Jun dalam mengatur proses pertumbuhan dan perkembangan sel, metabolism sel, diferensiasi dan apoptosis. Beberapa studi terkini menunjukkan bahwa FBXW7 berperan dalam perkembangan beberapa stem cell, mencakup proses self-renewal, multipotensi, diferensiasi, dan survival. Cancer stem cell (CSC) diketahui merupakan salah satu penyebab resistensi tumor terhadap berbagai kemoterapi, kekambuhan dan metastasis tumor. FBXW7 berperan terhadap kondisi quiescence pada CSC dengan mengatur substrat downstream c-Myc. Kondisi quiescence pada CSC dapat diinhibisi dengan memblokade peran FBXW7 melalui pathway upstream and downstream FBXW7 sehingga diharapkan dapat mengatasi resistensi dan kekambuhan tumor. Artikel telaah pustaka ini akan memaparkan peran FBXW7 pada stem cell normal dan pada cancer stem cell hubungannya dengan pengembangan terapi.
References
2. Wang L, Ye X, Liu Y, Wei W, Wang Z. Aberrant regulation of FBW7 in cancer. 2014;.
3. Cheng Y, Li G. Role of the ubiquitin ligase Fbw7 in cancer progression. Cancer and Metastasis Reviews. 2012;31(1-2):75–87.
4. Wang Z, Inuzuka H, Fukushima H, Wan L, Gao D, Shaik S, et al. Emerging roles of the FBW7 tumour suppressor in stem cell differentiation. EMBO reports. 2012;13(1):36–43.
5. Clevers H. The cancer stem cell: premises, promises and challenges. Nature medicine. 2011;p. 313–319.
6. Mao JH, Perez-losada J, Wu D, DelRosario R, Tsunematsu R, Nakayama KI, et al. Fbxw7/Cdc4 is a p53-dependent, haploinsufficient tumour suppressor gene. Nature. 2004;432(7018):775–779.
7. Sionov RV, Netzer E, Shaulian E. Differential regulation of FBXW7 isoforms by various stress stimuli. Cell Cycle. 2013;12(22):3547–3554.
8. Wang Z, Fukushima H, Gao D, Inuzuka H, Wan L, Lau AW, et al. The two faces of FBW7 in cancer drug resistance. Bioessays. 2011;33(11):851–859.
9. Wang Z, Inuzuka H, Zhong J, Wan L, Fukushima H, Sarkar FH, et al. Tumor suppressor functions of FBW7 in cancer development and progression. FEBS letters. 2012;586(10):1409–1418.
10. Takeishi S, Matsumoto A, Onoyama I, Naka K, Hirao A, Nakayama KI. Ablation of Fbxw7 eliminates leukemia-initiating cells by preventing quiescence. Cancer cell. 2013;23(3):347–361.
11. Cheng NC, Wang S, Young TH. The influence of spheroid formation of human adipose-derived stem cells on chitosan films on stemness and differentiation capabilities. Biomaterials. 2012;33(6):1748–1758.
12. Takeishi S. [Cell cycle regulation in cancer stem cells]. Nihon rinsho Japanese journal of clinical medicine. 2015;73(5):779–783.
13. Hoeck JD, Jandke A, Blake SM, Nye E, SpencerDene B, Brandner S, et al. Fbw7 controls neural stem cell differentiation and progenitor apoptosis via Notch and c-Jun. Nature neuroscience. 2010;13(11):1365–1372.
14. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. cell. 2006;126(4):663–676.
15. Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. nature. 2001;414(6859):105–111.
16. Izumi N, Helker C, Ehling M, Behrens A, Herzog W, Adams RH. Fbxw7 controls angiogenesis by regulating endothelial Notch activity. PloS one. 2012;7(7):e41116.
17. Morra F, Luise C, Merolla F, Poser I, Visconti R, Ilardi G, et al. FBXW7 and USP7 regulate CCDC6 turnover during the cell cycle and affect cancer drugs susceptibility in NSCLC. Oncotarget. 2015;6(14):12697.
