Top

Published in:

01-10-2012 | Research Article

JDP2 inhibits the epithelial-to-mesenchymal transition in pancreatic cancer BxPC3 cells

Authors: Zhe Liu, Ruixia Du, Jin Long, Anbing Dong, Jianpeng Fan, Kejian Guo, Yuanhong Xu

Published in: Tumor Biology | Issue 5/2012

Abstract

Pancreatic carcinoma is one of the most malignant and aggressive cancers. Increased motility and invasiveness of pancreatic cancer cells are believed to be associated with epithelial-to-mesenchymal transition (EMT). However, the molecular basis of EMT in pancreatic cancer cells is poorly understood. In this study, we examined the relationship between Jun dimerization protein 2 (JDP2), which is an AP-1 inhibitor, and EMT in human pancreatic carcinoma cells. We demonstrated that transforming growth factor-β1 (TGF-β1) promoted epidermal growth factor (EGF)-induced EMT in co-treated human pancreatic BxPC3 cells and that JDP2 overexpression reversed the EMT that was induced by co-treatment with TGF-β1 and EGF. These results suggest that EGF plays a principal role in EMT through its association with TGF-β1 in human pancreatic BxPC3 cells and that JDP2 may be a molecular target for pancreatic carcinoma intervention.

Jemal A, Siegel R, Ward E, et al. Cancer statistics. CA Cancer J Clin. 2006;56:106–30.CrossRefPubMed

Huang TC, Kar S, Javle M. Personalized therapy for pancreatic cancer: myth or reality in 2010? J Gastrointest Oncol. 2010;1:24–33.PubMedPubMedCentral

Kotowski A, Ma WW. Emerging therapies in pancreas cancer. J Gastrointest Oncol. 2011;2:93–103.PubMedPubMedCentral

Xiao DK, He JX. Epithelial mesenchymal transition and lung cancer. J Thorac Dis. 2010;2:154–9.PubMedPubMedCentral

Thiery JP. Epithelial–mesenchymal transitions in tumour progression. Nat Rev Cancer. 2002;2:442–54.CrossRefPubMed

Kang Y, Massagué J. Epithelial–mesenchymal transitions: twist in development and metastasis. Cell. 2004;118:277–9.CrossRefPubMed

Xie L, Law BK, Chytil AM, et al. Activation of the Erk pathway is required for TGF-beta1-induced EMT in vitro. Neoplasia (New York). 2004;6:603–10.CrossRef

Davies M, Robinson M, Smith E, et al. Induction of an epithelial to mesenchymal transition in human immortal and malignant keratinocytes by TGF-beta1 involves MAPK, Smad and AP-1 signalling pathways. J Cell Biochem. 2005;95:918–31.CrossRefPubMed

Aronheim A, Zandi E, Hennemann H, et al. Isolation of an AP-1 repressor by a novel method for detecting protein–protein interactions. Mol Cell Biol. 1997;17:3094–102.CrossRefPubMedPubMedCentral

10.

Jin C, Ugai H, Song J, et al. Identification of mouse Jun dimerization protein 2 as a novel repressor of ATF-2. FEBS Lett. 2001;489:34–41.CrossRefPubMed

11.

Kimura M. IRF2-binding protein-1 is a JDP2 ubiquitin ligase and an inhibitor of ATF2-dependent transcription. FEBS Lett. 2008;7:317–24.

12.

Ostrovsky O, Bengal E, Aronheim A. Induction of terminal differentiation by the c-Jun dimerization protein JDP2 in C2 myoblasts and rhabdomyosarcoma cells. J Biol Chem. 2002;277:40043–54.CrossRefPubMed

13.

Piu F, Aronheim A, Katz S, et al. AP-1 repressor protein JDP-2: inhibition of UV-mediated apoptosis through p53 down-regulation. Mol Cell Biol. 2001;21:3012–24.CrossRefPubMedPubMedCentral

14.

Bitton-Worms K, Pikarsky E, Aronheim A. The AP-1 repressor protein, JDP2, potentiates hepatocellular carcinoma in mice. Mol Cancer. 2010;9:54.CrossRefPubMedPubMedCentral

15.

Nakade K, Pan J, Yamasaki T, et al. JDP2 (Jun dimerization protein 2)-deficient mouse embryonic fibroblasts are resistant to replicative senescence. J Biol Chem. 2009;284:10808–17.CrossRefPubMedPubMedCentral

16.

Jin C, Kato K, Chimura T, et al. Regulation of histone acetylation and nucleosome assembly by transcription factor JDP2. Nat Struct Mol Biol. 2006;13:331–8.CrossRefPubMed

17.

Nishioka R, Itoh S, Gui T, et al. SNAIL induces epithelial-to-mesenchymal transition in a human pancreatic cancer cell line (BxPC3) and promotes distant metastasis and invasiveness in vivo. Exp Mol Pathol. 2010;89:149–57.CrossRefPubMed

18.

Cho SG, Yi Z, Pang X, et al. Kisspeptin-10, a KISS1-derived decapeptide, inhibits tumor angiogenesis by suppressing Sp1-mediated VEGF expression and FAK/Rho GTPase activation. Cancer Res. 2009;69:7062–70.CrossRefPubMedPubMedCentral

19.

Ellenrieder V, Hendler SF, Boeck W, et al. Transforming growth factor beta1 treatment leads to an epithelial–mesenchymal transdifferentiation of pancreatic cancer cells requiring extracellular signal-regulated kinase 2 activation. Cancer Res. 2001;61:4222–8.PubMed

20.

Heinrich R, Livne E, Ben-Izhak O, et al. The c-Jun dimerization protein 2 inhibits cell transformation and acts as a tumor suppressor gene. J Biol Chem. 2004;279:5708–15.CrossRefPubMed

21.

Jin C, Li H, Murata T, et al. JDP2, a repressor of AP-1, recruits an HDAC3 complex to inhibit the retinoic acid-induced differentiation of F9 cells. Mol Cell Biol. 2006;22:4815–26.CrossRef

22.

Weiss G, Rasmussen S, Nielsen Fink L. Bifidobacterium bifidum actively changes the gene expression profile induced by Lactobacillus acidophilus in murine dendritic cells. PLoS One. 2010;5:e11065.CrossRefPubMedPubMedCentral

23.

Wang P, Chen Z, Meng Z, et al. Dual role of Ski in pancreatic cancer cells: tumor-promoting versus metastasis-suppressive function. Carcinogenesis. 2009;30:1497–506.CrossRefPubMed

24.

Yasutome M, Gunn J, Korc M. Restoration of Smad4 in BxPC3 pancreatic cancer cells attenuates proliferation without altering angiogenesis. Clin Exp Metastasis. 2005;22:461–73.CrossRefPubMed

25.

Shintani Y, Hollingsworth MA, Wheelock MJ. Collagen I promotes metastasis in pancreatic cancer by activating c-Jun NH2-terminal kinase 1 and up-regulating N-cadherin expression. Cancer Res. 2006;66:11745–53.CrossRefPubMed

26.

Pan J, Yang M. The role of epithelial–mesenchymal transition in pancreatic cancer. J Gastrointest Oncol. 2011;2:151–6.PubMedPubMedCentral

27.

Thiery JP, Acloque H, Huang RY. Epithelial–mesenchymal transitions in development and disease. Cell. 2009;139:871–90.CrossRefPubMed

28.

Hsueh C. Pancreatic cancer: current standards, research updates and future directions. J Gastrointest Oncol. 2011;2:123–5.PubMedPubMedCentral

29.

Kikuta K, Masamune A, Watanabe T. Pancreatic stellate cells promote epithelial–mesenchymal transition in pancreatic cancer cells. Biochem Biophys Res Commun. 2010;403:380–4.CrossRefPubMed

30.

Onoue T, Uchida D, Begum NM. Epithelial–mesenchymal transition induced by the stromal cell-derived factor-1/CXCR4 system in oral squamous cell carcinoma cells. Int J Oncol. 2006;29:1133–8.PubMed

31.

Yuanhong X, Feng X, Qingchang L, et al. Downregulation of AP-1 repressor JDP2 is associated with tumor metastasis and poor prognosis in patients with pancreatic carcinoma. Int J Biol Markers. 2010;25:136–40.PubMed

32.

Lerdrup M, Holmberg C, Dietrich N, et al. Depletion of the AP-1 repressor JDP2 induces cell death similar to apoptosis. Biochim Biophys Acta. 2005;1745:29–37.CrossRefPubMed

33.

Pan J, Nakade K, Huang YC, et al. Suppression of cell-cycle progression by Jun dimerization protein-2 (JDP2) involves downregulation of cyclin-A2. Oncogene. 2010;29:6245–56.CrossRefPubMedPubMedCentral

34.

Benbrook DM, Jones NC. Heterodimer formation between CREB and JUN proteins. Oncogene. 1990;5:295–302.PubMed

35.

Jensen K, Afroze S, Munshi MK, et al. Mechanisms for nicotine in the development and progression of gastrointestinal cancers. Transl Gastrointest Cancer. 2012;1:81–7.PubMedPubMedCentral

36.

Berger AJ, Kluger HM, Li N, Kielhorn E, Halaban R, et al. Subcellular localization of activating transcription factor 2 in melanoma specimens predicts patient survival. Cancer Res. 2003;63:8103–7.PubMed

37.

Lee SH, Bahn JH, Whitlock NC, Baek SJ. Activating transcription factor 2 (ATF2) controls tolfenamic acid-induced ATF3 expression via MAP kinase pathways. Oncogene. 2010;29(37):5182–92.CrossRefPubMedPubMedCentral

Title: JDP2 inhibits the epithelial-to-mesenchymal transition in pancreatic cancer BxPC3 cells
Authors: Zhe Liu
Ruixia Du
Jin Long
Anbing Dong
Jianpeng Fan
Kejian Guo
Yuanhong Xu
Publication date: 01-10-2012
Publisher: Springer Netherlands
Published in: Tumor Biology / Issue 5/2012
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI: https://doi.org/10.1007/s13277-012-0404-5

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 5/2012

Differentially expressed proteins identified in overexpressed let-7a gastric carcinoma cells by two-dimensional polyacrylamide gel electrophoresis

The single nucleotide polymorphism g.1548A >G (K469E) of the ICAM-1 gene is associated with worse prognosis in non-small cell lung cancer

Identification of genes regulated by the EWS/NR4A3 fusion protein in extraskeletal myxoid chondrosarcoma

CCN1 promotes tumorigenicity through Rac1/Akt/NF-κB signaling pathway in pancreatic cancer

Diagnostic accuracy of tumour markers in serous effusions: a validation study

Nuclear p63 expression in osteoblastic tumors

Keynote webinar | Spotlight on antibody–drug conjugates in cancer