Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
International Journal of Clinical Oncology
Published in: International Journal of Clinical Oncology 6/2014

01-12-2014 | Original Article

The roles of Wnt5a, JNK and paxillin in the occurrence of metastasis of pancreatic adenocarcinoma

Authors: Wenli Lu, Wei Wei, Geertruida H. de Bock, Hongyuan Zhou, Qiang Li, Xiaohong Shen

Published in: International Journal of Clinical Oncology | Issue 6/2014

Login to get access

Abstract

Background

Wnt5a, p-JNK and p-paxillin proteins have been shown to be associated with the development of several types of cancer. Here we studied the role of Wnt5a, p-JNK and p-paxillin protein expressions and functions in the further development of pancreatic adenocarcinoma.

Methods

Fresh tissue samples from adjacent and malignant portions were obtained after operation from 58 patients with pancreatic adenocarcinoma. Wnt5a, p-JNK1, JNK1, paxillin and p-paxillin were detected with immunohistochemical staining.

Results

The expressions of Wnt5a, p-JNK1 and p-paxillin were higher in malignant tissues than in adjacent portions (p < 0.01), where JNK1 and paxillin were absent (p > 0.05). The expression levels of Wnt5a, p-JNK1 and p-paxillin in tumor tissues were correlated with each other (r = 0.564, 0.586 and 0.737, respectively). The expression of Wnt5a in tumor tissue could independently predict the occurrence of lymph node involvement [odds ratio (OR) 8.19, 95 % confidence interval (CI) 2.47–27.19]. The expression of p-JNK1 in tumor tissue was an independent predictor of peritoneal metastasis (OR 4.01, 95 % CI 1.32–12.17).

Conclusion

Wnt5a/JNK signaling might be activated in pancreatic cancer. Wnt5a is the specific predictor for lymph node involvement.
Literature
1.
Nieto J, Grossbard ML, Kozuch P (2008) Metastatic pancreatic cancer 2008: is the glass less empty? Oncologist 13:562–576PubMedCrossRef
2.
Funasaka T, Raz A (2007) The role of autocrine motility factor in tumor and tumor microenvironment. Cancer Metastasis Rev 26:725–735PubMedCrossRef
3.
Weeraratna AT, Jiang Y, Hostetter G et al (2002) Wnt5a signaling directly affects cell motility and invasion of metastatic melanoma. Cancer Cell 1:279–288PubMedCrossRef
4.
Bui TD, Zhang L, Rees MC et al (1997) Expression and hormone regulation of wnt2, 3, 4, 5a, 7a, 7b and 10b in normal human endometrium and endometrial carcinoma. Br J Cancer 75:1131–1136PubMedCentralPubMedCrossRef
5.
Blanc E, Goldschneider D, Douc-Rasy S et al (2005) Wnt-5a gene expression in malignant human neuroblasts. Cancer Lett 228:117–123PubMedCrossRef
6.
Liang H, Chen Q, Coles AH et al (2003) Wnt5a inhibits b cell proliferation and functions as a tumor suppressor in hematopoietic tissue. Cancer Cell 4:349–360PubMedCrossRef
7.
Kremenevskaja N, von Wasielewski R, Rao AS et al (2005) Wnt-5a has tumor suppressor activity in thyroid carcinoma. Oncogene 24:2144–2154PubMedCrossRef
8.
Jonsson M, Dejmek J, Bendahl PO et al (2002) Loss of wnt-5a protein is associated with early relapse in invasive ductal breast carcinomas. Cancer Res 62:409–416PubMed
9.
Roman-Gomez J, Jimenez-Velasco A, Cordeu L et al (2007) Wnt5a, a putative tumour suppressor of lymphoid malignancies, is inactivated by aberrant methylation in acute lymphoblastic leukaemia. Eur J Cancer 43:2736–2746PubMedCrossRef
10.
Da Forno PD, Pringle JH, Hutchinson P et al (2008) Wnt5a expression increases during melanoma progression and correlates with outcome. Clin Cancer Res 14:5825–5832PubMedCrossRef
11.
Pukrop T, Binder C (2008) The complex pathways of wnt 5a in cancer progression. J Mol Med (Berl) 86:259–266CrossRef
12.
Huang C, Rajfur Z, Borchers C et al (2003) JNK phosphorylates Paxillin and regulates cell migration. Nature 424:219–223PubMedCrossRef
13.
14.
Zeng ZY, Zhou YH, Zhang WL et al (2007) Gene expression profiling of nasopharyngeal carcinoma reveals the abnormally regulated Wnt signaling pathway. Hum Pathol 38:120–133PubMedCrossRef
15.
Fernandez-Cobo M, Zammarchi F, Mandeli J et al (2007) Expression of Wnt5a and Wnt10b in non-immortalized breast cancer cells. Oncol Rep 17:903–907PubMed
16.
Kurayoshi M, Oue N, Yamamoto H et al (2006) Expression of Wnt-5a is correlated with aggressiveness of gastric cancer by stimulating cell migration and invasion. Cancer Res 66:10439–10448PubMedCrossRef
17.
Yamauchi J, Miyamoto Y, Murabe M et al (2007) Gadd45a, the gene induced by the mood stabilizer valproic acid, regulates neurite outgrowth through JNK and the substrate Paxillin in N1e-115 neuroblastoma cells. Exp Cell Res 313:1886–1896PubMedCrossRef
18.
Ching YP, Leong VY, Lee MF et al (2007) P21-activated protein kinase is overexpressed in hepatocellular carcinoma and enhances cancer metastasis involving c-Jun NH2-terminal kinase activation and Paxillin phosphorylation. Cancer Res 67:3601–3608PubMedCrossRef
19.
Block ER, Matela AR, SundarRaj N et al (2004) Wounding induces motility in sheets of corneal epithelial cells through loss of spatial constraints: role of heparin-binding epidermal growth factor-like growth factor signaling. J Biol Chem 279:24307–24312PubMedCrossRef
20.
Kikuchi A, Yamamoto H, Sato A et al (2012) Wnt5a: its signalling, functions and implication in diseases. Acta Physiol (Oxf) 204:17–33CrossRef
21.
22.
23.
Iozzo RV, Eichstetter I, Danielson KG (1995) Aberrant expression of the growth factor Wnt-5a in human malignancy. Cancer Res 55:3495–3499PubMed
24.
Lejeune S, Huguet EL, Hamby A et al (1995) Wnt5a cloning, expression, and up-regulation in human primary breast cancers. Clin Cancer Res 1:215–222PubMed
25.
Smith K, Bui TD, Poulsom R et al (1999) Up-regulation of macrophage Wnt gene expression in adenoma-carcinoma progression of human colorectal cancer. Br J Cancer 81:496–502PubMedCentralPubMedCrossRef
26.
Sugiura T, Inoue Y, Matsuki R et al (2009) VEGF-C and VEGF-D expression is correlated with lymphatic vessel density and lymph node metastasis in oral squamous cell carcinoma: implications for use as a prognostic marker. Int J Oncol 34:673–680PubMedCrossRef
27.
Hirakawa S, Hong YK, Harvey N et al (2003) Identification of vascular lineage-specific genes by transcriptional profiling of isolated blood vascular and lymphatic endothelial cells. Am J Pathol 162:575–586PubMedCentralPubMedCrossRef
28.
Yin Y, Wang S, Sun Y et al (2009) JNK/AP-1 pathway is involved in tumor necrosis factor-alpha induced expression of vascular endothelial growth factor in MCF7 cells. Biomed Pharmacother 63:429–435PubMedCentralPubMedCrossRef
29.
Liu S, Xu SW, Kennedy L et al (2007) FAK is required for TGFbeta-induced JNK phosphorylation in fibroblasts: implications for acquisition of a matrix-remodeling phenotype. Mol Biol Cell 18:2169–2178PubMedCentralPubMedCrossRef
30.
Metadata
Title
The roles of Wnt5a, JNK and paxillin in the occurrence of metastasis of pancreatic adenocarcinoma
Authors
Wenli Lu
Wei Wei
Geertruida H. de Bock
Hongyuan Zhou
Qiang Li
Xiaohong Shen
Publication date
01-12-2014
Publisher
Springer Japan
Published in
International Journal of Clinical Oncology / Issue 6/2014
Print ISSN: 1341-9625
Electronic ISSN: 1437-7772
DOI
https://doi.org/10.1007/s10147-013-0648-0

Other articles of this Issue 6/2014

International Journal of Clinical Oncology 6/2014 Go to the issue

Original Article

Development of an integrated support system for hereditary cancer and its impact on gynecologic services

Original Article

A retrospective study of urokinase-type plasminogen activator receptor (uPAR) as a prognostic factor in cancer of the uterine cervix

Original Article

Paclitaxel–carboplatin for advanced or recurrent carcinosarcoma of the uterus: the Japan Uterine Sarcoma Group and Tohoku Gynecologic Cancer Unit Study

Original Article

Long-term changes in renal function outcomes following radical cystectomy and urinary diversion

Original Article

Pathology-oriented treatment strategy of malignant ovarian tumor in pregnant women: analysis of 41 cases in Japan

Original Article

Assessment of postoperative quality of life: comparative study between laparoscopic and minimum incision endoscopic radical prostatectomies
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
Image Credits