Skip to main content

Advertisement

SpringerLink
Log in

Derlin-1 is overexpressed in human colon cancer and promotes cancer cell proliferation

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Derlin-1 is overexpressed in many types of solid tumors and plays an important role in cancer progression. However, the expression pattern and functions of Derlin-1 in human colon cancer are not fully understood. In the present study, we examined Derlin-1 expression in colon cancer cell lines and human tissues and investigated its role in colon cancer. We found that Derlin-1 expression was increased significantly in colon cancer tissues and its overexpression correlated with the tumor differentiation, Dukes stage, invasion, lymph node metastasis, distant metastasis, and poor overall survival. The silencing of Derlin-1 by shRNA led to the growth inhibition of colon cancer cells, which were associated with the promotion of apoptosis. Furthermore, Derlin-1 silencing significantly inhibited the activation of the PI3K/AKT signaling pathway. Taken together, our results showed that Derlin-1 is overexpressed in colon cancer and promotes proliferation of colon cancer cells. Derlin-1 may be a potential therapeutic target for the treatment of colon 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
Fig. 5

Similar content being viewed by others

Abbreviations

ER:

Endoplasmic reticulum

NSCLC:

Non-small cell lung cancer

UPR:

Unfolded protein response

References

  1. Tenesa A, Dunlop MG (2009) New insights into the aetiology of colorectal cancer from genome-wide association studies. Nat Rev Genet 10:353–358. doi:10.1038/nrg2574

    Article  CAS  PubMed  Google Scholar 

  2. Schweiger MR, Hussong M, Rohr C, Lehrach H (2013) Genomics and epigenomics of colorectal cancer. Wiley Interdiscip Rev Syst Biol Med 5:205–219. doi:10.1002/wsbm.1206

    Article  CAS  PubMed  Google Scholar 

  3. Chen SF, Wu CH, Lee YM, Tam K, Tsai YC, Liou JY, Shyue SK (2013) Caveolin-1 interacts with Derlin-1 and promotes ubiquitination and degradation of cyclooxygenase-2 via collaboration with p97 complex. J Biol Chem 288:33462–33469. doi:10.1074/jbc.M113.521799

    Article  CAS  PubMed  Google Scholar 

  4. Wang F, Olson EM, Shyng SL (2012) Role of Derlin-1 protein in proteostasis regulation of ATP-sensitive potassium channels. J Biol Chem 287:10482–10493. doi:10.1074/jbc.M111.312223

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. Suzuki M, Otsuka T, Ohsaki Y, Cheng J, Taniguchi T, Hashimoto H, Taniguchi H, Fujimoto T (2012) Derlin-1 and UBXD8 are engaged in dislocation and degradation of lipidated ApoB-100 at lipid droplets. Mol Biol Cell 23:800–810. doi:10.1091/mbc.E11-11-0950

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Wang J, Hua H, Ran Y, Zhang H, Liu W, Yang Z, Jiang Y (2008) Derlin-1 is overexpressed in human breast carcinoma and protects cancer cells from endoplasmic reticulum stress-induced apoptosis. Breast Cancer Res 10:R7. doi:10.1186/bcr1849

    Article  PubMed Central  PubMed  Google Scholar 

  7. Dong QZ, Wang Y, Tang ZP, Fu L, Li QC, Wang ED, Wang EH (2013) Derlin-1 is overexpressed in non-small cell lung cancer and promotes cancer cell invasion via EGFR-ERK-mediated up-regulation of MMP-2 and MMP-9. Am J Pathol 182:954–964. doi:10.1016/j.ajpath.2012.11.019

    Article  CAS  PubMed  Google Scholar 

  8. Hu D, Ran YL, Zhong X, Hu H, Yu L, Lou JN, Sun LX, Yang ZH (2006) Overexpressed Derlin-1 inhibits ER expansion in the endothelial cells derived from human hepatic cavernous hemangioma. J Biochem Mol Biol 39:677–685

    Article  CAS  PubMed  Google Scholar 

  9. Ran Y, Hu H, Hu D, Zhou Z, Sun Y, Yu L, Sun L, Pan J, Liu J, Liu T, Yang Z (2008) Derlin-1 is overexpressed on the tumor cell surface and enables antibody-mediated tumor targeting therapy. Clin Cancer Res 14:6538–6545. doi:10.1158/1078-0432.CCR-08-0476

    Article  CAS  PubMed  Google Scholar 

  10. Klopfleisch R, Gruber AD (2009) Derlin-1 and stanniocalcin-1 are differentially regulated in metastasizing canine mammary adenocarcinomas. J Comp Pathol 141:113–120. doi:10.1016/j.jcpa.2008.09.010

    Article  CAS  PubMed  Google Scholar 

  11. Klopfleisch R, Schutze M, Linzmann H, Brunnberg L, Gruber AD (2010) Increased Derlin-1 expression in metastases of canine mammary adenocarcinomas. J Comp Pathol 142:79–83. doi:10.1016/j.jcpa.2009.06.006

    Article  CAS  PubMed  Google Scholar 

  12. Xu L, Wang ZH, Xu D, Lin G, Li DR, Wan T, Guo SL (2014) Expression of Derlin-1 and its effect on expression of autophagy marker genes under endoplasmic reticulum stress in lung cancer cells. Cancer Cell Int 14:50. doi:10.1186/1475-2867-14-50

    Article  PubMed Central  PubMed  Google Scholar 

  13. Ran Y, Jiang Y, Zhong X, Zhou Z, Liu H, Hu H, Lou JN, Yang Z (2006) Identification of derlin-1 as a novel growth factor-responsive endothelial antigen by suppression subtractive hybridization. Biochem Biophys Res Commun 348:1272–1278. doi:10.1016/j.bbrc.2006.07.186

    Article  CAS  PubMed  Google Scholar 

  14. Han YS, Lee JH, Lee SH (2015) Fucoidan inhibits the migration and proliferation of HT-29 human colon cancer cells via the phosphoinositide-3 kinase/Akt/mechanistic target of rapamycin pathways. Mol Med Rep. doi:10.3892/mmr.2015.3804

    Google Scholar 

  15. Fu R, Yang P, Wu HL, Li ZW, Li ZY (2014) GRP78 secreted by colon cancer cells facilitates cell proliferation via PI3 K/Akt signaling. Asian Pac J Cancer Prev 15:7245–7249

    Article  PubMed  Google Scholar 

  16. Liu YZ, Wu K, Huang J, Liu Y, Wang X, Meng ZJ, Yuan SX, Wang DX, Luo JY, Zuo GW, Yin LJ, Chen L, Deng ZL, Yang JQ, Sun WJ, He BC (2014) The PTEN/PI3 K/Akt and Wnt/beta-catenin signaling pathways are involved in the inhibitory effect of resveratrol on human colon cancer cell proliferation. Int J Oncol 45:104–112. doi:10.3892/ijo.2014.2392

    CAS  PubMed  Google Scholar 

  17. Bi M, Naczki C, Koritzinsky M, Fels D, Blais J, Hu N, Harding H, Novoa I, Varia M, Raleigh J, Scheuner D, Kaufman RJ, Bell J, Ron D, Wouters BG, Koumenis C (2005) ER stress-regulated translation increases tolerance to extreme hypoxia and promotes tumor growth. EMBO J 24:3470–3481. doi:10.1038/sj.emboj.7600777

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. Edagawa M, Kawauchi J, Hirata M, Goshima H, Inoue M, Okamoto T, Murakami A, Maehara Y, Kitajima S (2014) Role of activating transcription factor 3 (ATF3) in endoplasmic reticulum (ER) stress-induced sensitization of p53-deficient human colon cancer cells to tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis through up-regulation of death receptor 5 (DR5) by zerumbone and celecoxib. J Biol Chem 289:21544–21561. doi:10.1074/jbc.M114.558890

    Article  PubMed Central  PubMed  Google Scholar 

  19. Shimodaira Y, Takahashi S, Kinouchi Y, Endo K, Shiga H, Kakuta Y, Kuroha M, Shimosegawa T (2014) Modulation of endoplasmic reticulum (ER) stress-induced autophagy by C/EBP homologous protein (CHOP) and inositol-requiring enzyme 1alpha (IRE1alpha) in human colon cancer cells. Biochem Biophys Res Commun 445:524–533. doi:10.1016/j.bbrc.2014.02.054

    Article  CAS  PubMed  Google Scholar 

  20. Basile V, Belluti S, Ferrari E, Gozzoli C, Ganassi S, Quaglino D, Saladini M, Imbriano C (2013) bis-dehydroxy-curcumin triggers mitochondrial-associated cell death in human colon cancer cells through ER-stress induced autophagy. PLoS One 8:e53664. doi:10.1371/journal.pone.0053664

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Jakobsen CH, Storvold GL, Bremseth H, Follestad T, Sand K, Mack M, Olsen KS, Lundemo AG, Iversen JG, Krokan HE, Schonberg SA (2008) DHA induces ER stress and growth arrest in human colon cancer cells: associations with cholesterol and calcium homeostasis. J Lipid Res 49:2089–2100. doi:10.1194/jlr.M700389-JLR200

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Nishitoh H, Kadowaki H, Nagai A, Maruyama T, Yokota T, Fukutomi H, Noguchi T, Matsuzawa A, Takeda K, Ichijo H (2008) ALS-linked mutant SOD1 induces ER stress- and ASK1-dependent motor neuron death by targeting Derlin-1. Genes Dev 22:1451–1464. doi:10.1101/gad.1640108

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  23. Cho S, Lee M, Jun Y (2013) Forced interaction of cell surface proteins with Derlin-1 in the endoplasmic reticulum is sufficient to induce their dislocation into the cytosol for degradation. Biochem Biophys Res Commun 430:787–792. doi:10.1016/j.bbrc.2012.11.068

    Article  CAS  PubMed  Google Scholar 

  24. Cho S, Kim BY, Ahn K, Jun Y (2013) The C-terminal amino acid of the MHC-I heavy chain is critical for binding to Derlin-1 in human cytomegalovirus US11-induced MHC-I degradation. PLoS One 8:e72356. doi:10.1371/journal.pone.0072356

    Article  PubMed Central  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The work was supported by the National Natural Science Foundation of China (81172266), the Life Health Technology Foundation of Jiangsu province (BL2012031), and the Natural Science Foundation of Jiangsu province (BK2011859) to ZNF.

Author information

Author notes

    Authors and Affiliations

    1. Department of Gastroenterology, Nanjing Dachang Hospital, 68 Taizishan Rd, Yanjiang Industrial Development Zone, Nanjing, 210044, Jiangsu, China

      Xueming Tan

    2. Department of Apheresis, Nanjing Red Cross Blood Center, 3 Zizhulin, Nanjing, 210003, Jiangsu, China

      Xiaolu He

    3. Department of Gastroenterology, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiangjiayuan, Nanjing, 210011, Jiangsu, China

      Zhonghua Jiang, Xiaohong Wang & Limei Ma

    4. Department of Endoscopy Center, The First Affiliated of Hospital of Nanjing Medical University, 300 Guangzhou St., Nanjing, 210029, Jiangsu, China

      Li Liu, Xiang Wang & Zhining Fan

    5. The Metabolic Disease Research Centre, Nanjing Medical University, 140 Hanzhong St., Nanjing, 210029, Jiangsu, China

      Dongming Su

    Authors
    1. Xueming Tan
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Xiaolu He
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Zhonghua Jiang
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Xiaohong Wang
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Limei Ma
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. Li Liu
      View author publications

      You can also search for this author in PubMed Google Scholar

    7. Xiang Wang
      View author publications

      You can also search for this author in PubMed Google Scholar

    8. Zhining Fan
      View author publications

      You can also search for this author in PubMed Google Scholar

    9. Dongming Su
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding authors

    Correspondence to Zhining Fan or Dongming Su.

    Additional information

    Xueming Tan and Xiaolu He 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

    Tan, X., He, X., Jiang, Z. et al. Derlin-1 is overexpressed in human colon cancer and promotes cancer cell proliferation. Mol Cell Biochem 408, 205–213 (2015). https://doi.org/10.1007/s11010-015-2496-x

    Download citation

    • Received:

    • Accepted:

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s11010-015-2496-x

    Keywords

    Search

    Navigation