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Annexin A2 Enhances the Progression of Colorectal Cancer and Hepatocarcinoma via Cytoskeleton Structural Rearrangements

  • Huimin He (a1), Li Xiao (a1), Sinan Cheng (a1), Qian Yang (a1), Jinmei Li (a1), Yifan Hou (a1), Fengying Song (a1), Xiaorong Su (a1), Huijuan Jin (a1), Zheng Liu (a1), Jing Dong (a1), Ruiye Zuo (a1), Xigui Song (a1), Yanyan Wang (a1), Kun Zhang (a1), Wei Duan (a2) and Yingchun Hou (a1)...


Annexin A2 (ANXA2) is reported to be associated with cancer development. To investigate the roles ANXA2 plays during the development of cancer, the RNAi method was used to inhibit the ANXA2 expression in caco2 (human colorectal cancer cell line) and SMMC7721 (human hepatocarcinoma cell line) cells. The results showed that when the expression of ANXA2 was efficiently inhibited, the growth and motility of both cell lines were significantly decreased, and the development of the motility relevant microstructures, such as pseudopodia, filopodia, and the polymerization of microfilaments and microtubules were obviously inhibited. The cancer cell apoptosis was enhanced without obvious significance. The possible regulating pathway in the process was also predicted and discussed. Our results suggested that ANXA2 plays important roles in maintaining the malignancy of colorectal and hepatic cancer by enhancing the cell proliferation, motility, and development of the motility associated microstructures of cancer cells based on a possible complicated signal pathway.


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*Author for correspondence: Yingchun Hou, E-mail:


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Ağababaoğlu, İ, Önen, A, Demir, AB, Aktaş, S, Altun, Z, Ersöz, H, Şanl, A, Özdemir, N & Akkoçlu, A (2017). Chaperonin (HSP60) and annexin-2 are candidate biomarkers for non-small cell lung carcinoma. Medicine (Baltimore) 96(6), e5903.
Balch, C & Dedman, JR (1997). Annexins II and V inhibit cell migration. Exp Cell Res 237(2), 259263.
Benaud, C, Le Dez, G, Mironov, S, Galli, F, Reboutier, D & Prigent, C (2015). Annexin A2 is required for the early steps of cytokinesis. EMBO Rep 16(4), 481489.
Borthwick, LA, Riemen, C, Goddard, C, Colledge, WH, Mehta, A, Gerke, V & Muimo, R (2008). Defective formation of PKA/CnA-dependent annexin 2-S100A10/CFTR complex in DeltaF508 cystic fibrosis cells. Cell Signal 20(6), 10731083.
Bydoun, M & Waisman, DM (2014). On the contribution of S100A10 and annexin A2 to plasminogen activation and oncogenesis: An enduring ambiguity. Future Oncol 10(15), 24692479.
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(12), 23282341.
Chiang, Y, Schneiderman, MH & Vishwanatha, JK (1993). Annexin II expression is regulated during mammalian cell cycle. Cancer Res 53(24), 60176021.
Christensen, MV, Høgdall, CK, Jochumsen, KM & Høgdall, EVS (2018). Annexin A2 and cancer: A systematic review. Int J Oncol 52(1), 518.
Clifton, JG, Brown, MK, Huang, F, Li, X, Reutter, W, Hofmann, W, Hixson, DC & Josic, D (2006). Identification of members of the annexin family in the detergent-insoluble fraction of rat Morris hepatoma plasma membranes. J Chromatogr A 1123(2), 205211.
Defour, A, Medikayala, S, Van der Meulen, JH, Hogarth, MW, Holdreith, N, Malatras, A, Duddy, W, Boehler, J, Nagaraju, K & Jaiswal, JK (2017). Annexin A2 links poor myofiber repair with inflammation and adipogenic replacement of the injured muscle. Hum Mol Genet 26(11), 19791991.
Demonbreun, AR, Quattrocelli, M, Barefield, DY, Allen, MV, Swanson, KE & McNally, EM (2016). An actin-dependent annexin complex mediates plasma membrane repair in muscle. J Cell Biol 213(6), 705718.
El-Abd, N, Fawzy, A, Elbaz, T & Hamdy, S (2016). Evaluation of annexin A2 and as potential biomarkers for hepatocellular carcinoma. Tumour Biol 37(1), 211216.
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(5), 673685.
Fan, C, Fu, Z, Su, Q, Angelini, DJ, Van Eyk, J & Johns, RA (2011). S100a11 mediates hypoxia-induced mitogenic factor (HIMF)-induced smooth muscle cell migration, vesicular exocytosis, and nuclear activation. Mol Cell Proteomics 10(3), M110.000901.
Filipenko, NR & Waisman, DM (2001). The C terminus of annexin II mediates binding to F-actin. J Biol Chem 276(7), 53105315.
Gabel, M, Delavoie, F, Royer, C, Tahouly, T, Gasman, S, Bader, MF, Vitale, N & Chasserot-Golaz, S (2019). Phosphorylation cycling of Annexin A2 Tyr23 is critical for calcium-regulated exocytosis in neuroendocrine cells. Biochim Biophys Acta Mol Cell Res 1866(7), 12071217.
Gerke, V & Moss, SE (2002). Annexins: From structure to function. Physiol. Rev 82(2), 331371.
Guzmán-Aránguez, A, Olmo, N, Turnay, J, Lecona, E, Pérez-Ramos, P, López de Silanes, I & Lizarbe, MA (2005). Differentiation of human colon adenocarcinoma cells alters the expression and intracellular localization of annexins A1, A2, and A5. J Cell Biochem 94(1), 178193.
Hayes, MJ, Shao, D, Bailly, M & Moss, SE (2006). Regulation of actin dynamics by annexin 2. EMBO J 25(9), 18161826.
Huang, Y, Jin, Y, Yan, CH, Yu, Y, Bai, J, Chen, F, Zhao, YZ & Fu, SB (2008). Involvement of Annexin A2 in p53 induced apoptosis in lung cancer. Mol Cell Biochem 309(1–2), 117123.
Jaiswal, JK, Lauritzen, SP, Scheffer, L, Sakaguchi, M, Bunkenborg, J, Simon, SM, Kallunki, T, Jäättelä, M & Nylandsted, J (2014). S100a11 is required for efficient plasma membrane repair and survival of invasive cancer cells. Nat Commun 5, 3795.
Jaiswal, JK & Nylandsted, J (2015). S100 and annexin proteins identify cell membrane damage as the Achilles heel of metastatic cancer cells. Cell Cycle 14(4), 502509.
Jia, JW, Li, KL, Wu, JX & Guo, SL (2013). Clinical significance of annexin II expression in human non-small cell lung cancer. Tumour Biol 34(3), 17671771.
Jolly, C, Winfree, S, Hansen, B & Steele-Mortimer, O (2014). The Annexin A2/p11 complex is required for efficient invasion of Salmonella Typhimurium in epithelial cells. Cell Microbiol 16(1), 6477.
Kantara, C, O'Connell, MR, Luthra, G, Gajjar, A, Sarkar, S, Ullrich, RL & Singh, P (2015). Methods for detecting circulating cancer stem cells (CCSCs) as a novel approach for diagnosis of colon cancer relapse/metastasis. Lab Invest 95(1), 100112.
Kpetemey, M, Dasgupta, S, Rajendiran, S, Das, S, Gibbs, LD, Shetty, P, Gryczynski, Z & Vishwanatha, JK (2015). MIEN1, a novel interactor of Annexin A2, promotes tumor cell migration by enhancing AnxA2 cell surface expression. Mol Cancer 14, 156.
Kwaan, HC & Rego, EM (2010). Role of microparticles in the hemostatic dysfunction in acute promyelocytic leukemia. Semin Thromb Hemost 36(8), 917924.
Lauritzen, SP, Boye, TL & Nylandsted, J (2015). Annexins are instrumental for efficient plasma membrane repair in cancer cells. Semin Cell Dev Biol 45, 3238.
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(1), 3848.
Liu, J-W, Shen, J-J, Tanzillo-Swarts, A, Bhatia, B, Maldonado, CM, Person, MD, Lau, SS & Tang, DG (2003). Annexin II expression is reduced or lost in prostate cancer cells and its re-expression inhibits prostate cancer cell migration. Oncogene 22(10), 14751485.
Ma, S, Lu, CC, Yang, LY, Wang, JJ, Wang, BS, Cai, HQ, Hao, JJ, Xu, X, Cai, Y, Zhang, Y & Wang, MR (2018). ANXA2 promotes esophageal cancer progression by activating MYC-HIF1A-VEGF axis. J Exp Clin Cancer Res 37(1), 183.
Mai, J, Finley, RL Jr, Waisman, DM & Sloane, BF (2000). Human procathepsin B interacts with the annexin II tetramer on the surface of tumor cells. J Biol Chem 275(17), 1280612812.
Maji, S, Chaudhary, P, Akopova, I, Nguyen, PM, Hare, RJ, Gryczynski, I & Vishwanatha, JK (2017). Exosomal Annexin II promotes angiogenesis and breast cancer metastasis. Mol Cancer Res 15(1), 93105.
Pathak, A & Kumar, S (2011). Biophysical regulation of tumor cell invasion: Moving beyond matrix stiffness. Integr Biol (Camb) 3(4), 267278.
Pena-Alonso, E, Rodrigo, JP, Parra, IC, Pedrero, JM, Meana, MV, Nieto, CS, Fresno, MF, Morgan, RO & Fernandez, MP (2008). Annexin A2 localizes to the basal epithelial layer and is down-regulated in dysplasia and head and neck squamous cell carcinoma. Cancer Lett 263(1), 8998.
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(Pt 13), 21772185.
Ribatti, D (2017). A revisited concept: Contact inhibition of growth. From cell biology to malignancy. Exp Cell Res 359(1), 1719.
Sanz-Moreno, V & Marshall, CJ (2010). The plasticity of cytoskeletal dynamics underlying neoplastic cell migration. Curr Opin Cell Biol 22(5), 690696.
Siever, DA & Erickson, HP (1997). Extracellular annexin II. Int J Biochem Cell Biol 29(11), 12191223.
Singh, TK, Abonyo, B, Narasaraju, TA & Liu, L (2004). Reorganization of cytoskeleton during surfactant secretion in lung type II cells: A role of annexin II. Cell Signal 16(1), 6370.
Valapala, M & Vishwanatha, JK (2011). Lipid raft endocytosis and exosomal transport facilitate extracellular trafficking of annexin A2. J Biol Chem 286(35), 3091130925.
Vishwanatha, JK, Jindal, HK & Davis, RG (1992). The role of primer recognition proteins in DNA replication: Association with nuclear matrix in HeLa cells. J Cell Sci 101(Pt 1), 2534.
Wang, CY, Lin, YS, Su, WC, Chen, CL & Lin, CF (2009). Glycogen synthase kinase-3 and Omi/HtrA2 induce annexin A2 cleavage followed by cell cycle inhibition and apoptosis. Mol Biol Cell 20(19), 41534161.
Wang, S, Sun, H, Tanowitz, M, Liang, X-H & Stanley, T (2016). Crooke. Annexin A2 facilitates endocytic trafficking of antisense oligonucleotides. Nucleic Acids Res 44(15), 73147330.
Yamamoto, T, Kudo, M, Peng, WX, Takata, H, Takakura, H, Teduka, K, Fujii, T, Mitamura, K, Taga, A, Uchida, E & Naito, Z (2016). Identification of aldolase A as a potential diagnostic biomarker for colorectal cancer based on proteomic analysis using formalin-fixed paraffin-embedded tissue. Tumour Biol 37(10), 1359513606.
Zhai, H, Acharya, S, Gravanis, I, Mehmood, S, Seidman, RJ, Shroyer, KR, Hajjar, KA & Tsirka, SE (2011). Annexin A2 promotes glioma cell invasion and tumor progression. J Neurosci 31(40), 1434614360.
Zheng, L & Jaffee, EM (2012). Annexin A2 is a new antigenic target for pancreatic cancer immunotherapy. Oncoimmunology 1(1), 112114.
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Microscopy and Microanalysis
  • ISSN: 1431-9276
  • EISSN: 1435-8115
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