Gankyrin gene deletion followed by proteomic analysis: insight into the roles of Gankyrin in Tumorigenesis and Metastasis
详细信息 查看全文
- 作者：Xue Luo (1) (2)
Liang Chen (1)
Jiang Dai (1)
Yanfei Gao (1)
Hongli Wang (1)
Na Wang (1)
Yongqiang Zhao (1)
Feng Liu (1)
Zhihong Sang (1)
Jie Wang (1)
Weihua Li (1)
Kun He (1)
Baofeng Jin (1)
Jianghong Man (1)
Wei Zhang (3)
Qing Xia (1) - 刊名：BMC Medical Genomics
- 出版年：2012
- 出版时间：December 2012
- 年：2012
- 卷：5
- 期：1
- 全文大小：1071KB
- 参考文献：1. Lozano G, Zambetti GP: Gankyrin: an intriguing name for a novel regulator of p53 and RB. / Cancer Cell 2005,8(1):3-. CrossRef
2. Higashitsuji H, Itoh K, Nagao T, Dawson S, Nonoguchi K, Kido T, Mayer RJ, Arii S, Fujita J: Reduced stability of retinoblastoma protein by gankyrin, an oncogenic ankyrin-repeat protein overexpressed in hepatomas. / Nat Med 2000,6(1):96-9. CrossRef
3. Dong LW, Yang GZ, Pan YF, Chen Y, Tan YX, Dai RY, Ren YB, Fu J, Wang HY: The oncoprotein p28GANK establishes a positive feedback loop in beta-catenin signaling. / Cell Res 2011,21(8):1248-261. CrossRef
4. Higashitsuji H, Higashitsuji H, Itoh K, Sakurai T, Nagao T, Sumitomo H, Masuda T, Dawson S, Shimada Y, Mayer RJ, Fujita J: The oncoprotein gankyrin binds to MDM2/HDM2, enhancing ubiquitylation and degradation of p53. / Cancer Cell 2005,8(1):75-7. CrossRef
5. Man JH, Liang B, Gu YX, Zhou T, Li AL, Li T, Jin BF, Bai B, Zhang HY, Zhang WN, / et al.: Gankyrin plays an essential role in Ras-induced tumorigenesis through regulation of the RhoA/ROCK pathway in mammalian cells. / J Clin Invest 2010,120(8):2829-841. CrossRef
6. Meng Y, He L, Guo X, Tang S, Zhao X, Du R, Jin J, Bi Q, Li H, Nie Y, / et al.: Gankyrin promotes the proliferation of human pancreatic cancer. / Cancer Lett 2010,297(1):9-7. CrossRef
7. Tang S, Yang G, Meng Y, Du R, Li X, Fan R, Zhao L, Bi Q, Jin J, Gao L, / et al.: Overexpression of a novel gene gankyrin correlates with the malignant phenotype of colorectal cancer. / Cancer Biol Ther 2010,9(2):88-5. CrossRef
8. Jin BF, He K, Wang HX, Bai B, Zhou T, Li HY, Man JH, Liu BY, Gong WL, Wang J, / et al.: Proteomics analysis reveals insight into the mechanism of H-Ras-mediated transformation. / J Proteome Res 2006,5(10):2815-823. CrossRef
9. Rago C, Vogelstein B, Bunz F: Genetic knockouts and knockins in human somatic cells. / Nat Protoc 2007,2(11):2734-746. CrossRef
10. Jackson AL, Bartz SR, Schelter J, Kobayashi SV, Burchard J, Mao M, Li B, Cavet G, Linsley PS: Expression profiling reveals off-target gene regulation by RNAi. / Nat Biotechnol 2003,21(6):635-37. CrossRef
11. Bunz F, Dutriaux A, Lengauer C, Waldman T, Zhou S, Brown JP, Sedivy JM, Kinzler KW, Vogelstein B: Requirement for p53 and p21 to sustain G2 arrest after DNA damage. / Science 1998,282(5393):1497-501. CrossRef
12. Pan X, Zhao J, Zhang WN, Li HY, Mu R, Zhou T, Zhang HY, Gong WL, Yu M, Man JH, / et al.: Induction of SOX4 by DNA damage is critical for p53 stabilization and function. / Proc Natl Acad Sci USA 2009,106(10):3788-793. CrossRef
13. Jiang P, Du W, Wang X, Mancuso A, Gao X, Wu M, Yang X: p53 regulates biosynthesis through direct inactivation of glucose-6-phosphate dehydrogenase. / Nat Cell Biol 2011,13(3):310-16. CrossRef
14. Park BH, Vogelstein B, Kinzler KW: Genetic disruption of PPARdelta decreases the tumorigenicity of human colon cancer cells. / Proc Natl Acad Sci USA 2001,98(5):2598-603. CrossRef
15. Rajagopalan H, Jallepalli PV, Rago C, Velculescu VE, Kinzler KW, Vogelstein B, Lengauer C: Inactivation of hCDC4 can cause chromosomal instability. / Nature 2004,428(6978):77-1. CrossRef
16. Xia Q, Lu F, Yan HP, Wang HX, Feng X, Zhao Y, Liu BY, Wang J, Li P, Xue Y, / et al.: Autoantibody profiling of Chinese patients with autoimmune hepatitis using immunoproteomic analysis. / J Proteome Res 2008,7(5):1963-970. CrossRef
17. Wang X, Chen CF, Baker PR, Chen PL, Kaiser P, Huang L: Mass spectrometric characterization of the affinity-purified human 26S proteasome complex. / Biochemistry 2007,46(11):3553-565. CrossRef
18. Higashitsuji H, Itoh K, Sakurai T, Nagao T, Sumitomo Y, Masuda T, Dawson S, Shimada Y, Mayer RJ, Fujita J: The oncoprotein gankyrin binds to MDM2/HDM2, enhancing ubiquitylation and degradation of p53. / Cancer Cell 2005,8(1):75-7. CrossRef
19. Sidani M, Wessels D, Mouneimne G, Ghosh M, Goswami S, Sarmiento C, Wang W, Kuhl S, El-Sibai M, Backer JM, / et al.: Cofilin determines the migration behavior and turning frequency of metastatic cancer cells. / J Cell Biol 2007,179(4):777-91. CrossRef
20. Wang LH, Xiang J, Yan M, Zhang Y, Zhao Y, Yue CF, Xu J, Zheng FM, Chen JN, Kang Z, / et al.: The mitotic kinase Aurora-A induces mammary cell migration and breast cancer metastasis by activating the Cofilin-F-actin pathway. / Cancer Res 2010,70(22):9118-128. CrossRef
21. Lee S, Helfman DM: Cytoplasmic p21Cip1 is involved in Ras-induced inhibition of the ROCK/LIMK/cofilin pathway. / J Biol Chem 2004,279(3):1885-891. CrossRef
22. Wang W, Eddy R, Condeelis J: The cofilin pathway in breast cancer invasion and metastasis. / Nat Rev Cancer 2007,7(6):429-40. CrossRef
23. Lokman NA, Ween MP, Oehler MK, Ricciardelli C: The role of annexin A2 in tumorigenesis and cancer progression. / Cancer Microenviron 2011,4(2):199-08. CrossRef
24. Sharma MC, Sharma M: The role of annexin II in angiogenesis and tumor progression: a potential therapeutic target. / Curr Pharm Des 2007,13(35):3568-575. CrossRef
25. Yang X, Cao W, Zhang L, / et al.: Targeting 14--3zeta in cancer therapy. / Cancer Gene Ther 2012, 19:153-59. CrossRef
26. Gohla A, Bokoch GM: 14--3 regulates actin dynamics by stabilizing phosphorylated cofilin. / Curr Biol 2002, 12:1704-710. CrossRef
27. The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1755-8794/5/36/prepub - 作者单位：Xue Luo (1) (2)
Liang Chen (1)
Jiang Dai (1)
Yanfei Gao (1)
Hongli Wang (1)
Na Wang (1)
Yongqiang Zhao (1)
Feng Liu (1)
Zhihong Sang (1)
Jie Wang (1)
Weihua Li (1)
Kun He (1)
Baofeng Jin (1)
Jianghong Man (1)
Wei Zhang (3)
Qing Xia (1)
1. National Center of Biomedical Analysis, 27 Taiping Road, Beijing, 100850, China
2. Department of Occupational Health, Third Military Medical University, 30 Gaotanyan Road, Chongqing, 400038, China
3. Department of Clinical Laboratory, No. 307 Hospital, Academy of Military Medical Sciences, Beijing, 100071, China - ISSN：1755-8794
文摘
Background Gankyrin was originally purified and characterized as the p28 component of the 26S proteasome, and later identified as an oncogenic protein in hepatocellular carcinomas (HCC). It has recently been found to be highly expressed in several other malignancies, and compelling evidence show gankyrin plays important roles in tumorigenesis. However, its mechanism of action remains unclear. Methods In order to further clarify the functions of gankyrin and better understand its molecular mechanisms, we generated a gankyrin null cell line, HCT116 gankyrin??/sup> , by targeted homologous recombination in human colon cancer cells, and then employed two-dimensional electrophoresis (2-DE) based proteomic approaches followed by MS identification to investigate alterations in the proteome due to the gankyrin knockout. Western blot and qRT-PCR assays were also used to examine the protein and mRNA levels of some identified proteins. Results Compared with wild-type control cells, gankyrin null cells were impaired in terms of their proliferation, migration and anchorage-independent growth. A total of 21 altered proteins were identified, which included 18 proteins that had not previously been reported to be related to gankyrin. Notably, eight metastasis-related proteins were identified. Western blot analyses confirmed that the changes in three examined proteins were consistent with 2-DE gel analysis. Conclusions In summary, we have generated a useful cell tool to clarify the functions of gankyrin. Our proteomic data provide novel information to better understand the roles and underlying mechanisms by which gankyrin is involved in tumorigenesis and cancer metastasis.