Tumor Biology

, Volume 37, Issue 4, pp 5591–5597 | Cite as

BAG3 regulates cell proliferation, migration, and invasion in human colorectal cancer

  • Huiyong Shi
  • Haidong Xu
  • Zengjun Li
  • Yanan Zhen
  • Bin Wang
  • Shoujun Huo
  • Ruixue Xiao
  • Zhongfa XuEmail author
Original Article


Bcl2-associated athanogene 3 (BAG3) has been reported to be elevated in various tumors. However, it is unclear whether BAG3 has a functional role in the initiation and progression of colorectal cancer (CRC). Here, we collected CRC samples and cell lines to validate the pathway by using gene and protein assays. RT-PCR showed that the expression of BAG3 mRNA in CRC tissues was obviously higher than that in non-tumor tissues (p < 0.001). Immunohistochemical analysis showed that immunoreactivity of BAG3 was found in most CRC tissues and strongly correlated with TNM stage (p = 0.001), differentiation (p = 0.003), and metastasis (p = 0.010). Low expression of BAG3 in HCT-8 significantly reduced cellular proliferation, migration, and invasion. The analysis of in vitro cell showed that HCT-8 cells were exposed to si-BAG3, and its growth was inhibited depending on modulation of cell cycle G1/S checkpoints and cell cycle regulators, involving cyclin D1, cyclin A2, and cyclin B1. Furthermore, suppression of the epithelial-mesenchymal transition (EMT) by si-BAG3 is linked to the decreased expression of E-cadherin and the increased expression of N-cadherin, vimentin, and MMP9. In conclusion, in the present study, we demonstrated that BAG3 overexpression plays a critical role in cell proliferation, migration, and invasion of colorectal cancer. Our data suggests targeted inhibition of BAG3 may be useful for patients with CRC.





We greatly thank other members of our lab for valuable suggestions and writing.

Compliance with ethical standards

Conflicts of interest



  1. 1.
    Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.CrossRefPubMedGoogle Scholar
  2. 2.
    Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013;63:11–30.CrossRefPubMedGoogle Scholar
  3. 3.
    Mano MS, Duhoux F. Colon cancer: update on adjuvant therapy. Clin Colorectal Cancer. 2008;7:178–83.CrossRefPubMedGoogle Scholar
  4. 4.
    Gallagher DJ, Kemeny N. Metastatic colorectal cancer: from improved survival to potential cure. Oncology. 2010;78:237–48.CrossRefPubMedGoogle Scholar
  5. 5.
    Narayan S, Roy D. Role of APC and DNA mismatch repair genes in the development of colorectal cancers. Mol Cancer. 2003;2:41.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Boo YJ, Park JM, Kim J, et al. L1 expression as a marker for poor prognosis, tumour progression, and short survival in patients with colorectal cancer. Ann Surg Oncol. 2007;14:1703–11.CrossRefPubMedGoogle Scholar
  7. 7.
    Shi P, Fang C, Pang X. Astrocyte elevated gene-1 regulates CCL3/CCR5-induced epithelial-to-mesenchymal transition via Erk1/2 and Akt signaling in cardiac myxoma. Oncol Rep. 2015;34(3):1319–26.PubMedGoogle Scholar
  8. 8.
    Fuchs M, Poirier DJ, Seguin SJ, et al. Identification of the key structural motifs involved in HspB8/HspB6-Bag3 interaction. Biochem J. 2009;425(1):245–55.CrossRefPubMedGoogle Scholar
  9. 9.
    Gentilella A, Khalili K. Autoregulation of co-chaperone BAG3 gene transcription. J Cell Biochem. 2009;108(5):1117–24.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Zhu H, Wu W, Fu Y, et al. Overexpressed BAG3 is a potential therapeutic target in chronic lymphocytic leukemia. Ann Hematol. 2014;93(3):425–35.CrossRefPubMedGoogle Scholar
  11. 11.
    Festa M, Del Valle L, Khalili K, et al. BAG3 protein is overexpressed in human glioblastoma and is a potential target for therapy. Am J Pathol. 2011;178(6):2504–12.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Gentilella A, Khalili K. BAG3 expression in glioblastoma cells promotes accumulation of ubiquitinated clients in an Hsp70-dependent manner. J Biol Chem. 2011;286(11):9205–15.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Han G, Wu D, Yang Y, et al. CrkL meditates CCL20/CCR6-induced EMT in gastric cancer. Cytokine. 2015;76(2):163–9.CrossRefPubMedGoogle Scholar
  14. 14.
    Lv B, Yang X, Lv S, et al. CXCR4 signaling induced epithelial-mesenchymal transition by PI3K/AKT and ERK pathways in glioblastoma. Mol Neurobiol. 2015;52(3):1263–8.CrossRefPubMedGoogle Scholar
  15. 15.
    Liao A, Wang W, Sun D, et al. Bone morphogenetic protein 2 mediates epithelial-mesenchymal transition via AKT and ERK signaling pathways in gastric cancer. Tumour Biol. 2015;36(4):2773–8.CrossRefPubMedGoogle Scholar
  16. 16.
    Niu H, Yang X, Xu Z, et al. Cell surface nucleolin interacts with CXCR4 receptor via the 212 c-terminal portion. Tumour Biol. 2015;36(2):1099–104.CrossRefPubMedGoogle Scholar
  17. 17.
    Yang X, Lv S, Zhou X, et al. The clinical implications of transforming growth factor beta in pathological grade and prognosis of glioma patients: a meta-analysis. Mol Neurobiol. 2015;52(1):270–6.CrossRefPubMedGoogle Scholar
  18. 18.
    Pan Y, Zhang Y, Chen L, et al. The critical role of Rab31 in cell proliferation and apoptosis in cancer progression. Mol Neurobiol. 2015.Google Scholar
  19. 19.
    Li J, Li H, Liu J, et al. The clinical implications of human telomerase reverse transcriptase expression in grade and prognosis of gliomas: a systematic review and meta-analysis. Mol Neurobiol. 2015.Google Scholar
  20. 20.
    Ren G, Sheng L, Liu H, et al. The crucial role of SRPK1 in TGF-β-induced proliferation and apoptosis in the esophageal squamous cell carcinomas. Med Oncol. 2015;32(7):209.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Huiyong Shi
    • 1
  • Haidong Xu
    • 1
  • Zengjun Li
    • 2
  • Yanan Zhen
    • 1
  • Bin Wang
    • 1
  • Shoujun Huo
    • 1
  • Ruixue Xiao
    • 1
  • Zhongfa Xu
    • 1
    Email author
  1. 1.Department of General SurgeryAffiliated Hospital of Shandong Academy of Medical SciencesJinanChina
  2. 2.Department of General SurgeryShandong Cancer Hospital and InstituteJinanChina

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