Skip to main content

Advertisement

SpringerLink
Log in

Increased expression of MyD88 and association with paclitaxel resistance in breast cancer

  • Original Article
  • Published:
Tumor Biology

Abstract

MyD88 was reported to be associated with paclitaxel sensitivity in lung cancer; however, its roles in breast cancer remain unclear. The objective of this study is to investigate the expression and function of MyD88 in breast cancer. Immunohistochemistry (IHC) was used to analyze the expression of MyD88 in both breast cancer tissues and adjacent normal tissues. Real-time PCR and Western blots were further used to measure the messenger RNA (mRNA) and protein expression. The proliferation was assessed by WST-1. Flow cytometry was used to measure the cell cycle and apoptosis. The transwell assay was used to observe the change of migration and invasion of transfected cells. In breast cancer tissues, the expression of MyD88 was significantly higher than that in tumor-adjacent normal tissues (P < 0.001). MyD88 expression was found to be associated with the differentiation stages (P = 0.019). Kaplan-Meier survival curves showed statistically significant difference on survival in patients with high expression of MyD88 compared with those with normal expression of MyD88 (P = 0.018). Knockdown of MyD88 reduced the proliferation, migration, and invasion of MCF-7 cells and increased the sensitivity of MCF-7 cells to paclitaxel treatment through the inhibition of activation of NF-κB via PI3K/Akt. Our data indicate that MyD88 may be a potential target molecule to be used in diagnosis and treatment of breast cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69–90.

    Article  PubMed  Google Scholar 

  2. Hertz DL, Motsinger-Reif AA, Drobish A, Winham SJ, McLeod HL, Carey LA. DeesEC.CYP2C8*3 predicts benefit/risk profile in breast cancer patients receiving neoadjuvant paclitaxel. Cancer Res Treat. 2012;134(1):401–10.

    Article  CAS  Google Scholar 

  3. Belotti D, Vergani V, Drudis T, Borsotti P, Pitelli MR, Viale G, et al. The microtubule-affecting drug paclitaxel has antiangiogenic activity. Clin Cancer Res. 1996;2(11):1843–9.

    CAS  PubMed  Google Scholar 

  4. Risinger AL, Riffle SM, Lopus M, Jordan MA, Wilson L, Mooberry SL. The taccalonolides and paclitaxel cause distinct effects on microtubule dynamics and aster formation. Mol Cancer. 2014;13:41.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Gehrmann M, Schmidt M, Brase JC, Roos P, Hengstler JG. Prediction of paclitaxel resistance in breast cancer: is CYP1B1*3 a new factor of influence? Pharmacogenomics. 2008;9(7):969–74.

    Article  PubMed  Google Scholar 

  6. Jiang YZ, Yu KD, Peng WT, Di GH, Wu J, Liu GY, et al. Enriched variations in TEKT4 and breast cancer resistance to paclitaxel. Nat Commun. 2014;13(5):3802.

    Google Scholar 

  7. Coste I, Le Corf K, Kfoury A, Hmitou I, Druillennec S, Hainaut P, et al. Dual function of MyD88 in RAS signaling and inflammation, leading to mouse and human cell transformation. J Clin Invest. 2010;120(10):3663–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Kelly MG, Alvero AB, Chen R, Silasi DA, Abrahams VM, Chan S, et al. TLR-4 signaling promotes tumor growth and paclitaxel chemoresistance in ovarian cancer. Cancer Res. 2006;66:3859–68.

    Article  CAS  PubMed  Google Scholar 

  9. Szajnik M, Szczepanski MJ, Czystowska M, Elishaev E, Mandapathil M, Nowak-Markwitz E, et al. TLR4 signaling induced by lipopolysaccharide or paclitaxel regulates tumor survival and chemoresistance in ovarian cancer. Oncogene. 2009;28:4353–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Wang EL, Qian ZR, Nakasono M, Tanahashi T, Yoshimoto K, Bando Y, et al. High expression of Toll-like receptor 4/myeloid differentiation factor 88 signals correlates with poor prognosis in colorectal cancer. Br J Cancer. 2010;102:908–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Silasi DA, Alvero AB, Illuzzi J, Kelly M, Chen R, Fu HH, et al. MyD88 predicts chemoresistance to paclitaxel in epithelial ovarian cancer. Yale J Biol Med. 2006;79:153–63.

    CAS  PubMed  Google Scholar 

  12. Xiang FF, Wu R, Ni ZH, Pan CY, Zhan YP, Xu J, et al. MyD88 expression is associated with paclitaxel resistance in lung cancer A549 cells. Oncol Rep. 2014;32(5):1837–44.

    CAS  PubMed  Google Scholar 

  13. Holleman A, Chung I, Olsen RR, Kwak B, Mizokami A, Saijo N, et al. Mir-135a contributes to paclitaxel resistance in tumor cells both in vitro and in vivo. Oncogene. 2011;30(43):4386–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Rincon M, Broadwater G, Harris L, Crocker A, Weaver D, Dressler L, et al. Interleukin-6, multidrug resistance protein-1 expression and response to paclitaxel in women with metastatic breast cancer: results of cancer and leukemia group B trial 159806. Breast Cancer Res Treat. 2006;100(3):301–8.

    Article  CAS  PubMed  Google Scholar 

  15. Wang Y, Niu XL, Qu Y, Wu J, Zhu YQ, Sun WJ, et al. Autocrine production of interleukin-6 confers cisplatin and paclitaxel resistance in ovarian cancer cells. Cancer Lett. 2010;295(1):110–23.

    Article  CAS  PubMed  Google Scholar 

  16. Kawai T, Akira S. TLR signaling. Cell Death Differ. 2006;13:816–25.

    Article  CAS  PubMed  Google Scholar 

  17. Ozes ON, Mayo LD, Gustin JA, Pfeffer SR, Pfeffer LM, Donner DB. NFkappaB activation by tumour necrosis factor requires the Akt serinethreonine kinase. Nature. 1999;401:82–5.

    Article  CAS  PubMed  Google Scholar 

  18. Sizemore N, Leung S, Stark GR. Activation of phosphatidylinositol 3-kinase in response to interleukin-1 leads to phosphorylation and activation of the NF-kappaB p65/RelA subunit. Mol Cell Biol. 1999;19:4798–805.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Monick MM, Carter AB, Robeff PK, Flaherty DM, Peterson MW, Hunninghake GW. Lipopolysaccharide activates Akt in human alveolar macrophages resulting in nuclear accumulation and transcriptional activity of beta-catenin. J Immunol. 2001;166:4713–20.

    Article  CAS  PubMed  Google Scholar 

  20. Szczepanski MJ, Czystowska M, Szajnik M, Harasymczuk M, Boyiadzis M, Kruk-Zagajewska A, et al. Triggering of Toll-like receptor 4 expressed on human head and neck squamous cell carcinoma promotes tumor development and protects the tumor from immune attack. Cancer Res. 2009;69:3105–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Liang BB, Chen R, Wang T, Cao L, Liu YY, Yin F, et al. Myeloid differentiation factor 88 promotes growth and metastasis of human hepatocellular carcinoma. Clin Cancer Res. 2013;19:2905–16.

    Article  CAS  PubMed  Google Scholar 

  22. Smirnova T, Zhou ZN, Flinn RJ, Wyckoff J, Boimel PJ, Pozzuto M, et al. Phosphoinositide 3-kinase signaling is critical for ErbB3-driven breast cancer cell motility and metastasis. Oncogene. 2012;31(6):706–15.

    Article  CAS  PubMed  Google Scholar 

  23. Wu H, Windmiller DA, Wang L, Backer JM. YXXM motifs in the PDGF-β receptor serve dual roles as phosphoinositide 3-kinase binding motifs and tyrosine-based endocytic sorting signals. J Biol Chem. 2003;278(42):40425–8.

    Article  CAS  PubMed  Google Scholar 

  24. Vijapurkar U, Kim MS, Koland JG. Roles of mitogen-activated protein kinase and phosphoinositide 3’-kinase in ErbB2/ErbB3 coreceptor-mediated heregulin signaling. Exp Cell Res. 2003;284:291–302.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by grants from the Shanghai Municipal Health Bureau of China (no. 20134274), Shanghai Science and Technology Committee (no. 124119b1602) and Putuo Hospital, Shanghai University of Traditional Chinese Medicine (no. 2013GQ012I).

Author information

Author notes

    Authors and Affiliations

    1. Department of Laboratory Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, China

      Fenfen Xiang, Qianqian Kong, Jiemin Jiang, Rong Wu & Xiangdong Kang

    2. Central Lab, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, China

      Zhenhua Ni, Yueping Zhan & Jian Xu

    Authors
    1. Fenfen Xiang
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Zhenhua Ni
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Yueping Zhan
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Qianqian Kong
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Jian Xu
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. Jiemin Jiang
      View author publications

      You can also search for this author in PubMed Google Scholar

    7. Rong Wu
      View author publications

      You can also search for this author in PubMed Google Scholar

    8. Xiangdong Kang
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding authors

    Correspondence to Rong Wu or Xiangdong Kang.

    Additional information

    Fenfen Xiang, Zhenhua Ni and Yueping Zhan contributed equally to this work.

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Xiang, F., Ni, Z., Zhan, Y. et al. Increased expression of MyD88 and association with paclitaxel resistance in breast cancer. Tumor Biol. 37, 6017–6025 (2016). https://doi.org/10.1007/s13277-015-4436-5

    Download citation

    • Received:

    • Accepted:

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s13277-015-4436-5

    Keywords

    Search

    Navigation