Skip to main content
SpringerLink
Log in

PFDN1, an indicator for colorectal cancer prognosis, enhances tumor cell proliferation and motility through cytoskeletal reorganization

  • Original Paper
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

Prefoldin (PFDN) subunits have been reported upregulated in various tumor types, while the expression and functions of PFDN1 (PFDN subunit 1) in colorectal cancer (CRC) are not well elucidated. The aim of this study was to investigate the use of PFDN1 as a poor prognosis indicator for CRC and explore the functions of PFDN1 in CRC. The relationship between PFDN1 expression and CRC clinical-pathological statistics was detected on the tissue microarray containing 145 cases of CRC. ShRNA was used to silence PFDN1 expression in SW480 and RKO CRC cells, and these transfected cells were analyzed for changes in proliferation, colony formation, cell cycle, migration, and invasion. Immunofluorescence and immunoblot were used to determine the remodeling of the F-actin and α-tubulin. Finally, tumor growth on nude mice was observed and measured. In this study, we found PFDN1 was upregulated in CRC tissues compared with adjacent normal tissues. Also, PFDN1 expression positively correlated with tumor size and tumor invasion. Moreover, after silencing PFDN1 in SW480 and RKO cells, the proliferation and motility of CRC cells were significantly suppressed. The inhibitory effect of PFDN1 on tumor cell growth and motility was partially due to G2/M cell cycle blockage and cytoskeletal deficiency. Finally, in vivo assay showed that downregulation of PFDN1 inhibited tumor growth on nude mice and PFDN1 expression correlated with higher levels of Ki-67 staining. These findings indicate that PFDN1 was involved in the progression of CRC, and provide new insights into PFDN1 as a potential therapeutic target for CRC treatment.

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
Fig. 5
Fig. 6

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. Sun JK, Li X, Xing JJ, Cao F, Wang H, Gong HF, Zhang W. Lentivirus-mediated silencing of USO1 inhibits cell proliferation and migration of human colon cancer cells. Med Oncol. 2015;32:218.

    Article  Google Scholar 

  3. Ferlay J, Autier P, Boniol M, Heanue M, Colombet M, Boyle P. Estimates of the cancer incidence and mortality in Europe in 2006. Ann Oncol. 2007;18(3):581–92.

    Article  CAS  PubMed  Google Scholar 

  4. Zhao H, Dong T, Zhou H, Wang L, Huang A, Feng B, Quan Y, Jin R, Zhang W, Sun J, Zhang D, Zheng M. miR-320a suppresses colorectal cancer progression by targeting Rac1. Carcinogenesis. 2014;35(4):886–95.

    Article  CAS  PubMed  Google Scholar 

  5. Qian-Lin Z, Ting-Feng W, Qi-Feng C, Min-Hua Z, Ai-Guo L. Inhibition of cytosolic chaperonin CCTζ-1 expression depletes proliferation of colorectal carcinoma in vitro. J Surg Oncol. 2010;102(5):419–23.

    Article  PubMed  Google Scholar 

  6. Huang X, Wang X, Cheng C, Cai J, He S, Wang H, Liu F, Zhu C, Ding Z, Huang X, Zhang T, Zhang Y. Chaperonin containing TCP1, subunit 8 (CCT8) is upregulated in hepatocellular carcinoma and promotes HCC proliferation. APMIS. 2014;122(11):1070–9.

    CAS  PubMed  Google Scholar 

  7. Yokota S, Yamamoto Y, Shimizu K, Momoi H, Kamikawa T, Yamaoka Y, Yanagi H, Yura T, Kubota H. Increased expression of cytosolic chaperonin CCT in human hepatocellular and colonic carcinoma. Cell Stress Chaperones. 2001;6(4):345–50.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Siegers K, Waldmann T, Leroux MR, Grein K, Shevchenko A, Schiebel E, Hartl FU. Compartmentation of protein folding in vivo: sequestration of non-native polypeptide by the chaperonin-GimC system. EMBO J. 1999;18(1):75–84.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Siegert R, Leroux MR, Scheufler C, Hartl FU, Moarefi I. Structure of the molecular chaperone prefoldin: unique interaction of multiple coiled coil tentacles with unfolded proteins. Cell. 2000;103(4):621–32.

    Article  CAS  PubMed  Google Scholar 

  10. Martin-Benito J, Gomez-Reino J, Stirling PC, Lundin VF, Gomez-Puertas P, Boskovic J, Chacon P, Fernandez JJ, Berenguer J, Leroux MR, Valpuesta JM. Divergent substrate-binding mechanisms reveal an evolutionary specialization of eukaryotic prefoldin compared to its archaeal counterpart. Structure. 2007;15(1):101–10.

    Article  CAS  PubMed  Google Scholar 

  11. Hartl FU, Hayer-Hartl M. Converging concepts of protein folding in vitro and in vivo. Nat Struct Mol Biol. 2009;16(6):574–81.

    Article  CAS  PubMed  Google Scholar 

  12. Alldinger I, Dittert D, Peiper M, Fusco A, Chiappetta G, Staub E, Lohr M, Jesnowski R, Baretton G, Ockert D, Saeger HD, Grutzmann R, Pilarsky C. Gene expression analysis of pancreatic cell lines reveals genes overexpressed in pancreatic cancer. Pancreatology. 2005;5(4–5):370–9.

    Article  CAS  PubMed  Google Scholar 

  13. Cimmino F, Spano D, Capasso M, Zambrano N, Russo R, Zollo M, Iolascon A. Comparative proteomic expression profile in all-trans retinoic acid differentiated neuroblastoma cell line. J Proteome Res. 2007;6(7):2550–64.

    Article  CAS  PubMed  Google Scholar 

  14. Hansen WJ, Cowan NJ, Welch WJ. Prefoldin-nascent chain complexes in the folding of cytoskeletal proteins. J Cell Biol. 1999;145(2):265–77.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Martin-Benito J, Boskovic J, Gomez-Puertas P, Carrascosa JL, Simons CT, Lewis SA, Bartolini F, Cowan NJ, Valpuesta JM. Structure of eukaryotic prefoldin and of its complexes with unfolded actin and the cytosolic chaperonin CCT. EMBO J. 2002;21(23):6377–86.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. Brackley KI, Grantham J. Activities of the chaperonin containing TCP-1 (CCT): implications for cell cycle progression and cytoskeletal organisation. Cell Stress Chaperones. 2009;14(1):23–31.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Coghlin C, Carpenter B, Dundas SR, Lawrie LC, Telfer C, Murray GI. Characterization and over-expression of chaperonin t-complex proteins in colorectal cancer. J Pathol. 2006;210(3):351–7.

    Article  CAS  PubMed  Google Scholar 

  18. Nibbe RK, Markowitz S, Myeroff L, Ewing R, Chance MR. Discovery and scoring of protein interaction subnetworks discriminative of late stage human colon cancer. Mol Cell Proteomics. 2009;8(4):827–45.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Collins C, Volik S, Kowbel D, Ginzinger D, Ylstra B, Cloutier T, Hawkins T, Predki P, Martin C, Wernick M, Kuo WL, Alberts A, Gray JW. Comprehensive genome sequence analysis of a breast cancer amplicon. Genome Res. 2001;11(6):1034–42.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Miyoshi N, Ishii H, Mimori K, Nishida N, Tokuoka M, Akita H, Sekimoto M, Doki Y, Mori M. Abnormal expression of PFDN4 in colorectal cancer: a novel marker for prognosis. Ann Surg Oncol. 2010;17(11):3030–6.

    Article  PubMed  Google Scholar 

  21. Vainberg IE, Lewis SA, Rommelaere H, Ampe C, Vandekerckhove J, Klein HL, Cowan NJ. Prefoldin, a chaperone that delivers unfolded proteins to cytosolic chaperonin. Cell. 1998;93(5):863–73.

    Article  CAS  PubMed  Google Scholar 

  22. Miyazawa M, Tashiro E, Kitaura H, Maita H, Suto H, Iguchi-Ariga SM, Ariga H. Prefoldin subunits are protected from ubiquitin-proteasome system-mediated degradation by forming complex with other constituent subunits. J Biol Chem. 2011;286(22):19191–203.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  23. Zako T, Iizuka R, Okochi M, Nomura T, Ueno T, Tadakuma H, Yohda M, Funatsu T. Facilitated release of substrate protein from prefoldin by chaperonin. FEBS Lett. 2005;579(17):3718–24.

    Article  CAS  PubMed  Google Scholar 

  24. Lundin VF, Leroux MR, Stirling PC. Quality control of cytoskeletal proteins and human disease. Trends Biochem Sci. 2010;35(5):288–97.

    Article  CAS  PubMed  Google Scholar 

  25. Geissler S, Siegers K, Schiebel E. A novel protein complex promoting formation of functional alpha- and gamma-tubulin. EMBO J. 1998;17(4):952–66.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  26. Lundin VF, Srayko M, Hyman AA, Leroux MR. Efficient chaperone-mediated tubulin biogenesis is essential for cell division and cell migration in C. elegans. Dev Biol. 2008;313(1):320–34.

    Article  CAS  PubMed  Google Scholar 

  27. Grantham J, Brackley KI, Willison KR. Substantial CCT activity is required for cell cycle progression and cytoskeletal organization in mammalian cells. Exp Cell Res. 2006;312(12):2309–24.

    Article  CAS  PubMed  Google Scholar 

  28. Cao S, Carlesso G, Osipovich AB, Llanes J, Lin Q, Hoek KL, Khan WN, Ruley HE. Subunit 1 of the prefoldin chaperone complex is required for lymphocyte development and function. J Immunol. 2008;181(1):476–84.

    Article  CAS  PubMed  Google Scholar 

  29. O’Neill GM. The coordination between actin filaments and adhesion in mesenchymal migration. Cell Adhes Migr. 2009;3(4):355–7.

    Article  Google Scholar 

  30. Yamaguchi H, Condeelis J. Regulation of the actin cytoskeleton in cancer cell migration and invasion. Biochim Biophys Acta. 2007;1773(5):642–52.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  31. Huang HC, Shi J, Orth JD, Mitchison TJ. Evidence that mitotic exit is a better cancer therapeutic target than spindle assembly. Cancer Cell. 2009;16(4):347–58.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the National Natural Science Foundation (Grant No. 81201625); Basic Research Project of Shanghai Municipal Science and Technology Commission (Grant No. 13JC1404100); National High Technology Research and Development Program 863 (Grant No. 2012AA021103).

Author information

Author notes

    Authors and Affiliations

    1. Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

      Puxiongzhi Wang, Jingkun Zhao, Xiao Yang, Shaopei Guan, Jun Lu, Baochi Ou, Jing Sun, Yaping Zong, Bo Feng, Junjun Ma, Aiguo Lu & Minhua Zheng

    2. Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai, China

      Puxiongzhi Wang, Jingkun Zhao, Xiao Yang, Shaopei Guan, Jing Sun, Yaping Zong, Aiguo Lu & Minhua Zheng

    3. School of Medicine, University of Munich, Munich, Germany

      Hao Feng

    4. Department of Thoracic Surgery, Ruijin Hospital, Shanghai, China

      Dingpei Han & Runsen Jin

    Authors
    1. Puxiongzhi Wang
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Jingkun Zhao
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Xiao Yang
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Shaopei Guan
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Hao Feng
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. Dingpei Han
      View author publications

      You can also search for this author in PubMed Google Scholar

    7. Jun Lu
      View author publications

      You can also search for this author in PubMed Google Scholar

    8. Baochi Ou
      View author publications

      You can also search for this author in PubMed Google Scholar

    9. Runsen Jin
      View author publications

      You can also search for this author in PubMed Google Scholar

    10. Jing Sun
      View author publications

      You can also search for this author in PubMed Google Scholar

    11. Yaping Zong
      View author publications

      You can also search for this author in PubMed Google Scholar

    12. Bo Feng
      View author publications

      You can also search for this author in PubMed Google Scholar

    13. Junjun Ma
      View author publications

      You can also search for this author in PubMed Google Scholar

    14. Aiguo Lu
      View author publications

      You can also search for this author in PubMed Google Scholar

    15. Minhua Zheng
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding authors

    Correspondence to Junjun Ma or Aiguo Lu.

    Ethics declarations

    Conflict of interest

    The authors declare that they have no conflict of interest.

    Ethical approval

    All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.

    Informed consent

    Informed consent was obtained from all individual participants included in the study.

    Additional information

    Puxiongzhi Wang and Jingkun Zhao have 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

    Wang, P., Zhao, J., Yang, X. et al. PFDN1, an indicator for colorectal cancer prognosis, enhances tumor cell proliferation and motility through cytoskeletal reorganization. Med Oncol 32, 264 (2015). https://doi.org/10.1007/s12032-015-0710-z

    Download citation

    • Received:

    • Accepted:

    • Published:

    • DOI: https://doi.org/10.1007/s12032-015-0710-z

    Keywords

    Search

    Navigation