Breast Cancer Research and Treatment

, Volume 153, Issue 2, pp 263–275 | Cite as

RNAi-mediated silencing of Anxa2 inhibits breast cancer cell proliferation by downregulating cyclin D1 in STAT3-dependent pathway

  • Fei Zhang
  • Zhiyong Wang
  • Jie Yuan
  • Xiyin Wei
  • Ran Tian
  • Ruifang Niu
Preclinical study


Although the upregulated expression of Anxa2 has been implicated in carcinogenesis, cancer progression, and poor prognosis of cancer patients, the detailed molecular mechanisms involved in these processes remain unclear. In this study, we investigated the effect of Anxa2 downregulation with small interference RNA on breast cancer proliferation. To explore molecular mechanisms underlying Anxa2-mediated cancer cell proliferation. We analyzed cell cycle distribution and signaling pathways using semi-quantitative real-time PCR and Western blotting. Anxa2 depletion in breast cancer cells significantly inhibited cell proliferation by decelerating cell cycle progression. The retarded G1-to-S phase transition in Anxa2-silenced cells was attributed to the decreased levels of cyclin D1, which is a crucial promoting factor for cell proliferation because it regulates G1-to-S phase transition during cell cycle progression. We provided evidence that Anxa2 regulates epidermal growth factor-induced phosphorylation of STAT3. The reduced expression of phosphorylated STAT3 is the main factor responsible for decreased cyclin D1 levels in Anxa2-silenced breast cancer cells. Our results revealed the direct relationship between Anxa2 and activation of STAT3, a key transcription factor that plays a pivotal role in regulating breast cancer proliferation and survival. This study provides novel insights into the functions of Anxa2 as a critical molecule in cellular signal transduction and significantly improves our understanding of the mechanism through which Anxa2 regulates cell cycle and cancer cell proliferation.


Anxa2 Breast cancer Proliferation Cyclin D1 STAT3 



This research was supported by grants from the National Natural Science Foundation of China (Nos. 81372844, and 81472474), Tianjin Municipal Science and Technology Commission (Nos. 12JCZDJC24500 and 12JCQNJC07000), Changjiang Scholars and Innovative Research Team (IRT1076), 863 Project (2012AA020206-5), Specialized Research Fund for the Doctoral Program of Higher Education (20131202110002).

Compliance with ethical standards

Conflict of Interest

The authors declare that they have no conflict of interest.


  1. 1.
    Balmanno K, Cook SJ (1999) Sustained MAP kinase activation is required for the expression of cyclin D1, p21Cip1 and a subset of AP-1 proteins in CCL39 cells. Oncogene 18:3085–3097. doi: 10.1038/sj.onc.1202647 CrossRefPubMedGoogle Scholar
  2. 2.
    Bao H, Jiang M, Zhu M, Sheng F, Ruan J, Ruan C (2009) Overexpression of Annexin II affects the proliferation, apoptosis, invasion and production of proangiogenic factors in multiple myeloma. Int J Hematol 90:177–185. doi: 10.1007/s12185-009-0356-8 CrossRefPubMedGoogle Scholar
  3. 3.
    Bharadwaj A, Bydoun M, Holloway R, Waisman D (2013) Annexin A2 heterotetramer: structure and function. Int J Mol Sci 14:6259–6305. doi: 10.3390/ijms14036259 PubMedCentralCrossRefPubMedGoogle Scholar
  4. 4.
    Bromberg JF, Wrzeszczynska MH, Devgan G, Zhao Y, Pestell RG, Albanese C, Darnell JE Jr (1999) Stat3 as an oncogene. Cell 98:295–303. doi: 10.1016/S0092-8674(00)81959-5 CrossRefPubMedGoogle Scholar
  5. 5.
    Chaudhary P, Thamake SI, Shetty P, Vishwanatha JK (2014) Inhibition of triple-negative and Herceptin-resistant breast cancer cell proliferation and migration by Annexin A2 antibodies. Br J Cancer 111:2328–2341. doi: 10.1038/bjc.2014.542 CrossRefPubMedGoogle Scholar
  6. 6.
    Chuthapisith S, Bean BE, Cowley G, Eremin JM, Samphao S, Layfield R, Kerr ID, Wiseman J, El-Sheemy M, Sreenivasan T, Eremin O (2009) Annexins in human breast cancer: possible predictors of pathological response to neoadjuvant chemotherapy. Eur J Cancer 45:1274–1281. doi: 10.1016/j.ejca.2013.12.002 CrossRefPubMedGoogle Scholar
  7. 7.
    De Graauw M, Cao L, Winkel L, van Miltenburg MH, le Devedec SE, Klop M, Yan K, Pont C, Rogkoti VM, Tijsma A, Chaudhuri A, Lalai R, Price L, Verbeek F, van de Water B (2013) Annexin A2 depletion delays EGFR endocytic trafficking via cofilin activation and enhances EGFR signaling and metastasis formation. Oncogene. doi: 10.1038/onc.2013.219 PubMedGoogle Scholar
  8. 8.
    Duncan R, Carpenter B, Main LC, Telfer C, Murray GI (2008) Characterisation and protein expression profiling of annexins in colorectal cancer. Br J Cancer 98:426–433PubMedCentralCrossRefPubMedGoogle Scholar
  9. 9.
    Emoto K, Sawada H, Yamada Y, Fujimoto H, Takahama Y, Ueno M, Takayama T, Uchida H, Kamada K, Naito A, Hirao S, Nakajima Y (2001) Annexin II overexpression is correlated with poor prognosis in human gastric carcinoma. Anticancer Res 21:1339–1345PubMedGoogle Scholar
  10. 10.
    Emoto K, Yamada Y, Sawada H, Fujimoto H, Ueno M, Takayama T, Kamada K, Naito A, Hirao S, Nakajima Y (2001) Annexin II overexpression correlates with stromal tenascin-C overexpression: a prognostic marker in colorectal carcinoma. Cancer 92:1419–1426. doi: 10.1002/1097-0142 CrossRefPubMedGoogle Scholar
  11. 11.
    Esposito I, Penzel R, Chaib-Harrireche M, Barcena U, Bergmann F, Riedl S, Kayed H, Giese N, Kleeff J, Friess H, Schirmacher P (2006) Tenascin C and annexin II expression in the process of pancreatic carcinogenesis. J Pathol 208:673–685. doi: 10.1002/path.1935 CrossRefPubMedGoogle Scholar
  12. 12.
    Filipenko NR, MacLeod TJ, Yoon CS, Waisman DM (2004) Annexin A2 is a novel RNA-binding protein. J Biol Chem 279:8723–8731. doi: 10.1074/jbc.M311951200 CrossRefPubMedGoogle Scholar
  13. 13.
    Gao H, Yu B, Yan Y, Shen J, Zhao S, Zhu J, Qin W, Gao Y (2013) Correlation of expression levels of ANXA2, PGAM1, and CALR with glioma grade and prognosis. J Neurosurg 118:846–853. doi: 10.3171/2012.9.JNS112134 CrossRefPubMedGoogle Scholar
  14. 14.
    Gao N, Flynn DC, Zhang Z, Zhong XS, Walker V, Liu KJ, Shi X, Jiang BH (2004) G1 cell cycle progression and the expression of G1 cyclins are regulated by PI3 K/AKT/mTOR/p70S6K1 signaling in human ovarian cancer cells. Am J Physiol Cell Physiol 287:C281–C291. doi: 10.1152/ajpcell.00422.2003 CrossRefPubMedGoogle Scholar
  15. 15.
    Gao N, Zhang Z, Jiang BH, Shi X (2003) Role of PI3 K/AKT/mTOR signaling in the cell cycle progression of human prostate cancer. Biochem Biophys Res Commun 310:1124–1132CrossRefPubMedGoogle Scholar
  16. 16.
    Gerke V, Weber K (1984) Identity of p36 K phosphorylated upon Rous sarcoma virus transformation with a protein purified from brush borders; calcium-dependent binding to non-erythroid spectrin and F-actin. EMBO J 3:227–233PubMedCentralPubMedGoogle Scholar
  17. 17.
    Glenney JR Jr, Tack BF (1985) Amino-terminal sequence of p36 and associated p10: identification of the site of tyrosine phosphorylation and homology with S-100. Proc Natl Acad Sci USA 82:7884–7888PubMedCentralCrossRefPubMedGoogle Scholar
  18. 18.
    Hsieh FC, Cheng G, Lin J (2005) Evaluation of potential Stat3-regulated genes in human breast cancer. Biochem Biophys Res Commun 335:292–299. doi: 10.1016/j.bbrc.2005.07.075 CrossRefPubMedGoogle Scholar
  19. 19.
    Ishii Y, Waxman S, Germain D (2008) Tamoxifen stimulates the growth of cyclin D1-overexpressing breast cancer cells by promoting the activation of signal transducer and activator of transcription 3. Cancer Res 68:852–860. doi: 10.1158/0008-5472.CAN-07-2879 CrossRefPubMedGoogle Scholar
  20. 20.
    Jin L, Shen Q, Ding S, Jiang W, Jiang L, Zhu X (2012) Immunohistochemical expression of Annexin A2 and S100A proteins in patients with bulky stage IB-IIA cervical cancer treated with neoadjuvant chemotherapy. Gynecol Oncol 126:140–146. doi: 10.1016/j.ygyno.2012.04.005 CrossRefPubMedGoogle Scholar
  21. 21.
    Kagawa S, Takano S, Yoshitomi H, Kimura F, Satoh M, Shimizu H, Yoshidome H, Ohtsuka M, Kato A, Furukawa K, Matsushita K, Nomura F, Miyazaki M (2012) Akt/mTOR signaling pathway is crucial for gemcitabine resistance induced by Annexin II in pancreatic cancer cells. J Surg Res 178:758–767. doi: 10.1016/j.jss.2012.05.065 CrossRefPubMedGoogle Scholar
  22. 22.
    Klein EA, Assoian RK (2008) Transcriptional regulation of the cyclin D1 gene at a glance. J Cell Sci 121:3853–3857. doi: 10.1242/jcs.039131 PubMedCentralCrossRefPubMedGoogle Scholar
  23. 23.
    Lavoie JN, L’Allemain G, Brunet A, Muller R, Pouyssegur J (1996) Cyclin D1 expression is regulated positively by the p42/p44MAPK and negatively by the p38/HOGMAPK pathway. J Biol Chem 271:20608–20616CrossRefPubMedGoogle Scholar
  24. 24.
    Leslie K, Gao SP, Berishaj M, Podsypanina K, Ho H, Ivashkiv L, Bromberg J (2010) Differential interleukin-6/Stat3 signaling as a function of cellular context mediates Ras-induced transformation. Breast Cancer Res 12:R80. doi: 10.1186/bcr2725 PubMedCentralCrossRefPubMedGoogle Scholar
  25. 25.
    Leslie K, Lang C, Devgan G, Azare J, Berishaj M, Gerald W, Kim YB, Paz K, Darnell JE, Albanese C, Sakamaki T, Pestell R, Bromberg J (2006) Cyclin D1 is transcriptionally regulated by and required for transformation by activated signal transducer and activator of transcription 3. Cancer Res 66:2544–2552. doi: 10.1158/0008-5472.CAN-05-2203 CrossRefPubMedGoogle Scholar
  26. 26.
    Ling Q, Jacovina AT, Deora A, Febbraio M, Simantov R, Silverstein RL, Hempstead B, Mark WH, Hajjar KA (2004) Annexin II regulates fibrin homeostasis and neoangiogenesis in vivo. J Clin Invest 113:38–48. doi: 10.1172/JCI19684 PubMedCentralCrossRefPubMedGoogle Scholar
  27. 27.
    Lokman NA, Ween MP, Oehler MK, Ricciardelli C (2011) The role of annexin A2 in tumorigenesis and cancer progression. Cancer Microenviron 4:199–208. doi: 10.1007/s12307-011-0064-9 PubMedCentralCrossRefPubMedGoogle Scholar
  28. 28.
    Luo CH, Liu QQ, Zhang PF, Li MY, Chen ZC, Liu YF (2013) Prognostic significance of annexin II expression in non-small cell lung cancer. Clin Trans Oncol 15:938–946. doi: 10.1007/s12094-013-1028-y CrossRefGoogle Scholar
  29. 29.
    Mohammad HS, Kurokohchi K, Yoneyama H, Tokuda M, Morishita A, Jian G, Shi L, Murota M, Tani J, Kato K, Miyoshi H, Deguchi A, Himoto T, Usuki H, Wakabayashi H, Izuishi K, Suzuki Y, Iwama H, Deguchi K, Uchida N, Sabet EA, Arafa UA, Hassan AT, El-Sayed AA, Masaki T (2008) Annexin A2 expression and phosphorylation are up-regulated in hepatocellular carcinoma. Int J Oncol 33:1157–1163PubMedGoogle Scholar
  30. 30.
    Musgrove EA, Caldon CE, Barraclough J, Stone A, Sutherland RL (2011) Cyclin D as a therapeutic target in cancer. Nat Rev Cancer 11:558–572. doi: 10.1038/nrc3090 CrossRefPubMedGoogle Scholar
  31. 31.
    Musgrove EA, Lee CS, Buckley MF, Sutherland RL (1994) Cyclin D1 induction in breast cancer cells shortens G1 and is sufficient for cells arrested in G1 to complete the cell cycle. Proc Natl Acad Sci USA 91:8022–8026PubMedCentralCrossRefPubMedGoogle Scholar
  32. 32.
    Ohno Y, Izumi M, Kawamura T, Nishimura T, Mukai K, Tachibana M (2009) Annexin II represents metastatic potential in clear-cell renal cell carcinoma. Br J Cancer 101:287–294PubMedCentralCrossRefPubMedGoogle Scholar
  33. 33.
    Parrales A, Lopez E, Lee-Rivera I, Lopez-Colome AM (2013) ERK1/2-dependent activation of mTOR/mTORC1/p70S6 K regulates thrombin-induced RPE cell proliferation. Cell Signal 25:829–838. doi: 10.1016/j.cellsig.2012.12.023 CrossRefPubMedGoogle Scholar
  34. 34.
    Quelle DE, Ashmun RA, Shurtleff SA, Kato JY, Bar-Sagi D, Roussel MF, Sherr CJ (1993) Overexpression of mouse D-type cyclins accelerates G1 phase in rodent fibroblasts. Genes Dev 7:1559–1571CrossRefPubMedGoogle Scholar
  35. 35.
    Rescher U, Ludwig C, Konietzko V, Kharitonenkov A, Gerke V (2008) Tyrosine phosphorylation of annexin A2 regulates Rho-mediated actin rearrangement and cell adhesion. J Cell Sci 121:2177–2185CrossRefPubMedGoogle Scholar
  36. 36.
    Sasser AK, Sullivan NJ, Studebaker AW, Hendey LF, Axel AE, Hall BM (2007) Interleukin-6 is a potent growth factor for ER-alpha-positive human breast cancer. FASEB J 21:3763–3770. doi: 10.1096/fj.07-8832com CrossRefPubMedGoogle Scholar
  37. 37.
    Saxena NK, Vertino PM, Anania FA, Sharma D (2007) leptin-induced growth stimulation of breast cancer cells involves recruitment of histone acetyltransferases and mediator complex to CYCLIN D1 promoter via activation of Stat3. J Biol Chem 282:13316–13325. doi: 10.1074/jbc.M609798200 PubMedCentralCrossRefPubMedGoogle Scholar
  38. 38.
    Semov A, Moreno MJ, Onichtchenko A, Abulrob A, Ball M, Ekiel I, Pietrzynski G, Stanimirovic D, Alakhov V (2005) Metastasis-associated protein S100A4 induces angiogenesis through interaction with Annexin II and accelerated plasmin formation. J Biol Chem 280:20833–20841. doi: 10.1074/jbc.M412653200 CrossRefPubMedGoogle Scholar
  39. 39.
    Sharma M, Blackman MR, Sharma MC (2012) Antibody-directed neutralization of annexin II (ANX II) inhibits neoangiogenesis and human breast tumor growth in a xenograft model. Exp Mol Pathol 92:175–184. doi: 10.1016/j.yexmp.2011.10.003 CrossRefPubMedGoogle Scholar
  40. 40.
    Sharma M, Ownbey RT, Sharma MC (2010) Breast cancer cell surface annexin II induces cell migration and neoangiogenesis via tPA dependent plasmin generation. Exp Mol Pathol 88:278–286CrossRefPubMedGoogle Scholar
  41. 41.
    Sharma MR, Koltowski L, Ownbey RT, Tuszynski GP, Sharma MC (2006) Angiogenesis-associated protein annexin II in breast cancer: selective expression in invasive breast cancer and contribution to tumor invasion and progression. Exp Mol Pathol 81:146–156CrossRefPubMedGoogle Scholar
  42. 42.
    Shetty PK, Thamake SI, Biswas S, Johansson SL, Vishwanatha JK (2012) Reciprocal regulation of annexin A2 and EGFR with Her-2 in Her-2 negative and herceptin-resistant breast cancer. PLoS One 7:e44299. doi: 10.1371/journal.pone.0044299 PubMedCentralCrossRefPubMedGoogle Scholar
  43. 43.
    Shi Y, Sharma A, Wu H, Lichtenstein A, Gera J (2005) Cyclin D1 and c-myc internal ribosome entry site (IRES)-dependent translation is regulated by AKT activity and enhanced by rapamycin through a p38 MAPK- and ERK-dependent pathway. J Biol Chem 280:10964–10973. doi: 10.1074/jbc.M407874200 CrossRefPubMedGoogle Scholar
  44. 44.
    Shiozawa Y, Havens AM, Jung Y, Ziegler AM, Pedersen EA, Wang J, Lu G, Roodman GD, Loberg RD, Pienta KJ, Taichman RS (2008) Annexin II/annexin II receptor axis regulates adhesion, migration, homing, and growth of prostate cancer. J Cell Biochem 105:370–380. doi: 10.1002/jcb.21835 PubMedCentralCrossRefPubMedGoogle Scholar
  45. 45.
    Takano S, Togawa A, Yoshitomi H, Shida T, Kimura F, Shimizu H, Yoshidome H, Ohtsuka M, Kato A, Tomonaga T, Nomura F, Miyazaki M (2008) Annexin II overexpression predicts rapid recurrence after surgery in pancreatic cancer patients undergoing gemcitabine-adjuvant chemotherapy. Ann Surg Oncol 15:3157–3168. doi: 10.1245/s10434-008-0061-5 CrossRefPubMedGoogle Scholar
  46. 46.
    Velasco-Velazquez MA, Li Z, Casimiro M, Loro E, Homsi N, Pestell RG (2011) Examining the role of cyclin D1 in breast cancer. Future Oncol 7:753–765. doi: 10.2217/fon.11.56 CrossRefPubMedGoogle Scholar
  47. 47.
    Wang CY, Chen CL, Tseng YL, Fang YT, Lin YS, Su WC, Chen CC, Chang KC, Wang YC, Lin CF (2012) Annexin A2 silencing induces G2 arrest of non-small cell lung cancer cells through p53-dependent and -independent mechanisms. J Biol Chem 287:32512–32524. doi: 10.1074/jbc.M112.351957 PubMedCentralCrossRefPubMedGoogle Scholar
  48. 48.
    Wang CY, Lin CF (2014) Annexin A2: its molecular regulation and cellular expression in cancer development. Dis Markers 2014:308976. doi: 10.1155/2014/308976 PubMedCentralPubMedGoogle Scholar
  49. 49.
    Wang TC, Cardiff RD, Zukerberg L, Lees E, Arnold A, Schmidt EV (1994) Mammary hyperplasia and carcinoma in MMTV-cyclin D1 transgenic mice. Nature 369:669–671. doi: 10.1038/369669a0 CrossRefPubMedGoogle Scholar
  50. 50.
    Wang YQ, Zhang F, Tian R, Ji W, Zhou Y, Sun XM, Liu Y, Wang ZY, Niu RF (2012) Tyrosine 23 phosphorylation of Annexin A2 promotes proliferation, invasion, and Stat3 phosphorylation in the nucleus of human breast cancer SK-BR-3 Cells. Cancer Biol Med 9:248–253. doi: 10.7497/j.issn.2095-3941.2012.04.005 PubMedCentralPubMedGoogle Scholar
  51. 51.
    Wu B, Zhang F, Yu M, Zhao P, Ji W, Zhang H, Han J, Niu R (2012) Up-regulation of Anxa2 gene promotes proliferation and invasion of breast cancer MCF-7 cells. Cell Prolif 45:189–198. doi: 10.1111/j.1365-2184.2012.00820.x CrossRefPubMedGoogle Scholar
  52. 52.
    Yao H, Zhang Z, Xiao Z, Chen Y, Li C, Zhang P, Li M, Liu Y, Guan Y, Yu Y, Chen Z (2009) Identification of metastasis associated proteins in human lung squamous carcinoma using two-dimensional difference gel electrophoresis and laser capture microdissection. Lung Cancer 65:41–48CrossRefPubMedGoogle Scholar
  53. 53.
    Yu GR, Kim SH, Park SH, Cui XD, Xu DY, Yu HC, Cho BH, Yeom YI, Kim SS, Kim SB, Chu IS (2007) Kim DG (2007) Identification of molecular markers for the oncogenic differentiation of hepatocellular carcinoma. Exp Mol Med 39:641–652CrossRefPubMedGoogle Scholar
  54. 54.
    Yu H, Pardoll D, Jove R (2009) STATs in cancer inflammation and immunity: a leading role for STAT3. Nat Rev Cancer 9:798–809CrossRefPubMedGoogle Scholar
  55. 55.
    Yu Q, Geng Y, Sicinski P (2001) Specific protection against breast cancers by cyclin D1 ablation. Nature 411:1017–1021. doi: 10.1038/35082500 CrossRefPubMedGoogle Scholar
  56. 56.
    Zhang F, Liu Y, Wang Z, Sun X, Yuan J, Wang T, Tian R, Ji W, Yu M, Zhao Y, Niu R (2015) A novel Anxa2-interacting protein Ebp1 inhibits cancer proliferation and invasion by suppressing Anxa2 protein level. Mol Cell Endocrinol 411:75–85. doi: 10.1016/j.mce.2015.04.013 CrossRefPubMedGoogle Scholar
  57. 57.
    Zhang F, Zhang H, Wang Z, Yu M, Tian R, Ji W, Yang Y, Niu R (2014) P-glycoprotein associates with Anxa2 and promotes invasion in multidrug resistant breast cancer cells. Biochem Pharmacol 87:292–302. doi: 10.1016/j.bcp.2013.11.003 CrossRefPubMedGoogle Scholar
  58. 58.
    Zhang F, Zhang L, Zhang B, Wei X, Yang Y, Qi RZ, Ying G, Zhang N, Niu R (2009) Anxa2 plays a critical role in enhanced invasiveness of the multidrug resistant human breast cancer cells. J Proteome Res 8:5041–5047. doi: 10.1021/pr900461c CrossRefPubMedGoogle Scholar
  59. 59.
    Zhang W, Zhao P, Xu XL, Cai L, Song ZS, Cao DY, Tao KS, Zhou WP, Chen ZN, Dou KF (2013) Annexin A2 promotes the migration and invasion of human hepatocellular carcinoma cells in vitro by regulating the shedding of CD147-harboring microvesicles from tumor cells. PLoS One 8:e67268. doi: 10.1371/journal.pone.0067268 PubMedCentralCrossRefPubMedGoogle Scholar
  60. 60.
    Zhang X, Liu S, Guo C, Zong J, Sun MZ (2012) The association of annexin A2 and cancers. Clin Trans Oncol 14:634–640. doi: 10.1007/s12094-012-0855-6 CrossRefGoogle Scholar
  61. 61.
    Zhao P, Zhang W, Tang J, Ma X, Dai J, Li Y, Jiang J, Zhang S, Chen Z (2010) Annexin II promotes invasion and migration of human hepatocellular carcinoma cells in vitro via its interaction with HAb18G/CD147. Cancer Sci 101:387–395CrossRefPubMedGoogle Scholar
  62. 62.
    Zhao P, Zhang W, Wang SJ, Yu XL, Tang J, Huang W, Li Y, Cui HY, Guo YS, Tavernier J, Zhang SH, Jiang JL, Chen ZN (2011) HAb18G/CD147 promotes cell motility by regulating annexin II-activated RhoA and Rac1 signaling pathways in hepatocellular carcinoma cells. Hepatology 54:2012–2024. doi: 10.1002/hep.24592 CrossRefPubMedGoogle Scholar
  63. 63.
    Zheng L, Foley K, Huang L, Leubner A, Mo G, Olino K, Edil BH, Mizuma M, Sharma R, Le DT, Anders RA, Illei PB, Van Eyk JE, Maitra A, Laheru D, Jaffee EM (2011) Tyrosine 23 phosphorylation-dependent cell-surface localization of annexin A2 is required for invasion and metastases of pancreatic cancer. PLoS One 6:e19390. doi: 10.1371/journal.pone.0019390 PubMedCentralCrossRefPubMedGoogle Scholar
  64. 64.
    Zhou S, Yi T, Liu R, Bian C, Qi X, He X, Wang K, Li J, Zhao X, Huang C, Wei Y (2012) Proteomics identification of annexin A2 as a key mediator in the metastasis and proangiogenesis of endometrial cells in human adenomyosis. Mol Cell Proteomics 11(M112):017988. doi: 10.1074/mcp.M112.017988 PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Fei Zhang
    • 1
    • 2
  • Zhiyong Wang
    • 1
    • 2
  • Jie Yuan
    • 1
    • 2
  • Xiyin Wei
    • 1
    • 2
  • Ran Tian
    • 1
    • 2
  • Ruifang Niu
    • 1
    • 2
  1. 1.Public Laboratory, Key Laboratory of Breast Cancer Prevention and Therapy, Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for CancerTianjin Medical UniversityTianjinPeople’s Republic of China
  2. 2.Key Laboratory of Cancer Prevention and TherapyTianjinPeople’s Republic of China

Personalised recommendations