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DIAPH3 promoted the growth, migration and metastasis of hepatocellular carcinoma cells by activating beta-catenin/TCF signaling

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Abstract

The enhanced ability of cancer cell migration and metastasis is the major cause for the cancer-related death of hepatocellular carcinoma (HCC). Better understanding the mechanisms for the motility of cancer cells will benefit the treatment. Diaphanous-related formin 3 (DIAPH3) has been reported to regulate the motility of cells by remodeling the cytoskeleton. However, the mechanism through which DIAPH3 regulated the motility of cancer cells remains largely unknown. In this study, we have shown that the expression of DIAPH3 was up-regulated in HCC. DIAPH3 positively regulated the growth, migration, colony formation, epithelia mesenchymal transition, and metastasis of HCC cells. Mechanically, DIAPH3 activated the beta-catenin/TCF signaling by binding HSP90 and disrupting the interaction between GSK3beta and HSP90. Taken together, our study demonstrated the oncogenic activity of DIAPH3 in the progression of HCC and suggested that PDIAPH3 might be a therapeutic target.

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References

  1. Katoh M, Katoh M (2004) Identification and characterization of human FHOD3 gene in silico. Int J Mol Med 13:615–620

    CAS  PubMed  Google Scholar 

  2. Wicki A, Lehembre F, Wick N, Hantusch B, Kerjaschki D, Christofori G (2006) Tumor invasion in the absence of epithelial-mesenchymal transition: podoplanin-mediated remodeling of the actin cytoskeleton. Cancer Cell 9:261–272

    Article  CAS  PubMed  Google Scholar 

  3. Ocana OH, Corcoles R, Fabra A, Moreno-Bueno G, Acloque H, Vega S, Barrallo-Gimeno A, Cano A, Nieto MA (2012) Metastatic colonization requires the repression of the epithelial-mesenchymal transition inducer Prrx1. Cancer Cell 22:709–724

    Article  CAS  PubMed  Google Scholar 

  4. Serresi M, Gargiulo G, Proost N, Siteur B, Cesaroni M, Koppens M, Xie H, Sutherland KD, Hulsman D, Citterio E, Orkin S, Berns A, van Lohuizen M (2016) Polycomb repressive complex 2 is a barrier to KRAS-driven inflammation and epithelial-mesenchymal transition in non-small-cell lung cancer. Cancer Cell 29:17–31

    Article  CAS  PubMed  Google Scholar 

  5. He X (2006) Unwinding a path to nuclear beta-catenin. Cell 127:40–42

    Article  CAS  PubMed  Google Scholar 

  6. Jessen JR, Solnica-Krezel L (2005) Axis formation–beta-catenin catches a Wnt. Cell 120:736–737

    Article  CAS  PubMed  Google Scholar 

  7. Macdonald BT, Semenov MV, He X (2007) SnapShot: Wnt/beta-catenin signaling. Cell 131:1204

    Article  CAS  PubMed  Google Scholar 

  8. Surel C, Guillet M, Lenoir M, Bourien J, Sendin G, Joly W, Delprat B, Lesperance MM, Puel JL, Nouvian R (2016) Remodeling of the inner hair cell microtubule meshwork in a mouse model of auditory neuropathy AUNA1. eNeuro. doi:10.1523/ENEURO.0295-16.2016

    PubMed  PubMed Central  Google Scholar 

  9. Calvo F, Ege N, Grande-Garcia A, Hooper S, Jenkins RP, Chaudhry SI, Harrington K, Williamson P, Moeendarbary E, Charras G, Sahai E (2013) Mechanotransduction and YAP-dependent matrix remodelling is required for the generation and maintenance of cancer-associated fibroblasts. Nat Cell Biol 15:637–646

    Article  CAS  PubMed  Google Scholar 

  10. Schoen CJ, Burmeister M, Lesperance MM (2013) Diaphanous homolog 3 (Diap3) overexpression causes progressive hearing loss and inner hair cell defects in a transgenic mouse model of human deafness. PLoS ONE 8:e56520

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Schoen CJ, Emery SB, Thorne MC, Ammana HR, Sliwerska E, Arnett J, Hortsch M, Hannan F, Burmeister M, Lesperance MM (2010) Increased activity of Diaphanous homolog 3 (DIAPH3)/diaphanous causes hearing defects in humans with auditory neuropathy and in Drosophila. Proc Natl Acad Sci USA 107:13396–13401

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Katoh M, Katoh M (2004) Identification and characterization of human FHOD3 gene in silico. Int J Mol Med 13:615–620

    CAS  PubMed  Google Scholar 

  13. Lin YN, Windhorst S (2016) Diaphanous-related formin 1 as a target for tumor therapy. Biochem Soc Trans 44:1289–1293

    Article  CAS  PubMed  Google Scholar 

  14. Hager MH, Morley S, Bielenberg DR, Gao S, Morello M, Holcomb IN, Liu W, Mouneimne G, Demichelis F, Kim J, Solomon KR, Adam RM, Isaacs WB, Higgs HN, Vessella RL, Di Vizio D, Freeman MR (2012) DIAPH3 governs the cellular transition to the amoeboid tumour phenotype. EMBO Mol Med 4:743–760

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Cooper LC, Prinsloo E, Edkins AL, Blatch GL (2011) Hsp90alpha/beta associates with the GSK3beta/axin1/phospho-beta-catenin complex in the human MCF-7 epithelial breast cancer model. Biochem Biophys Res Commun 413:550–554

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported by the Nature Science Foundation of Inner Mongolia (2015MS08144) and National Science Foundation (Grant No. 8123406).

Author contributions

LD and RG designed this project. ZL, LX, GL, CZ, ZC, HL performed the experiments.

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Authors and Affiliations

  1. Department of Medical Oncology, Inner Mongolia People’s Hospital, Hohhot, Inner Mongolia, China

    Li Dong, Liying Xue, Cuiying Zhang, Zhihui Cai & Hui Li

  2. Department of Radiation Therapy, Inner Mongolia People’s Hospital, Hohhot, Inner Mongolia, China

    Zhijun Li

  3. Inner Mongolia Medical University Graduate School, Hohhot, Inner Mongolia, China

    Gang Li

  4. Clinical Nutrition Center, Inner Mongolia People’s Hospital, 20 Zhaowuda Road, Saihan District, Hohhot, 010017, Inner Mongolia, China

    Ruifang Guo

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  1. Li Dong
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  2. Zhijun Li
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  3. Liying Xue
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  4. Gang Li
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  5. Cuiying Zhang
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  6. Zhihui Cai
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  7. Hui Li
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  8. Ruifang Guo
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Correspondence to Ruifang Guo.

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The authors declare that they have no conflict of interest.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

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Dong, L., Li, Z., Xue, L. et al. DIAPH3 promoted the growth, migration and metastasis of hepatocellular carcinoma cells by activating beta-catenin/TCF signaling. Mol Cell Biochem 438, 183–190 (2018). https://doi.org/10.1007/s11010-017-3125-7

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  • DOI: https://doi.org/10.1007/s11010-017-3125-7

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