Skip to main content
Top
Published in: Medical Oncology 3/2015

01-03-2015 | Original Paper

Capn4 promotes non-small cell lung cancer progression via upregulation of matrix metalloproteinase 2

Authors: Jie Gu, Feng-kai Xu, Guang-yin Zhao, Chun-lai Lu, Zong-wu Lin, Jian-yong Ding, Di Ge

Published in: Medical Oncology | Issue 3/2015

Login to get access

Abstract

The expression of calpain small subunit 1 (Capn4) is correlated with the invasion of several types of tumors. However, the roles of Capn4 in non-small cell lung cancer (NSCLC) remain unclear. In this study, we found that the expression of Capn4 in NSCLC tissues was much higher than that in nontumorous samples. High levels of Capn4 expression were associated with lymph node metastasis and large tumor size in NSCLC patients. The 5-year overall survival rate in the Capn4high group was significantly lower than that in the Capn4low group. In multivariate analysis, Capn4 was identified as an independent prognostic factor for overall survival. Moreover, in an in vitro analysis, downregulation of Capn4 expression by siRNA suppressed the invasive potential of lung cancer cells. Finally, we demonstrated that Capn4 enhanced the invasion ability of lung cancer cells by upregulating the expression of matrix metalloproteinase 2. Our findings indicated that Capn4 may represent a potential therapeutic target and a novel prognostic marker of NSCLC.
Appendix
Available only for authorised users
Literature
1.
2.
go back to reference Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127(12):2893–917.CrossRefPubMed Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127(12):2893–917.CrossRefPubMed
3.
go back to reference Hanna RA, Campbell RL, Davies PL. Calcium-bound structure of calpain and its mechanism of inhibition by calpastatin. Nature. 2008;456(7220):409–12.CrossRefPubMed Hanna RA, Campbell RL, Davies PL. Calcium-bound structure of calpain and its mechanism of inhibition by calpastatin. Nature. 2008;456(7220):409–12.CrossRefPubMed
4.
5.
go back to reference Franco SJ, Huttenlocher A. Regulating cell migration: calpains make the cut. J Cell Sci. 2005;118(Pt 17):3829–38.CrossRefPubMed Franco SJ, Huttenlocher A. Regulating cell migration: calpains make the cut. J Cell Sci. 2005;118(Pt 17):3829–38.CrossRefPubMed
6.
go back to reference Storr SJ, Carragher NO, Frame MC, Parr T, Martin SG. The calpain system and cancer. Nat Rev Cancer. 2011;11(5):364–74.CrossRefPubMed Storr SJ, Carragher NO, Frame MC, Parr T, Martin SG. The calpain system and cancer. Nat Rev Cancer. 2011;11(5):364–74.CrossRefPubMed
7.
go back to reference Lee SJ, Choi YL, Lee EJ, Kim BG, Bae DS, Ahn GH, et al. Increased expression of calpain 6 in uterine sarcomas and carcinosarcomas: an immunohistochemical analysis. Int J Gynecol Cancer. 2007;17(1):248–53.CrossRefPubMed Lee SJ, Choi YL, Lee EJ, Kim BG, Bae DS, Ahn GH, et al. Increased expression of calpain 6 in uterine sarcomas and carcinosarcomas: an immunohistochemical analysis. Int J Gynecol Cancer. 2007;17(1):248–53.CrossRefPubMed
8.
go back to reference Mamoune A, Luo JH, Lauffenburger DA, Wells A. Calpain-2 as a target for limiting prostate cancer invasion. Cancer Res. 2003;63(15):4632–40.PubMed Mamoune A, Luo JH, Lauffenburger DA, Wells A. Calpain-2 as a target for limiting prostate cancer invasion. Cancer Res. 2003;63(15):4632–40.PubMed
9.
go back to reference Bai DS, Dai Z, Zhou J, Liu YK, Qiu SJ, Tan CJ, et al. Capn4 overexpression underlies tumor invasion and metastasis after liver transplantation for hepatocellular carcinoma. Hepatology. 2009;49(2):460–70.CrossRefPubMed Bai DS, Dai Z, Zhou J, Liu YK, Qiu SJ, Tan CJ, et al. Capn4 overexpression underlies tumor invasion and metastasis after liver transplantation for hepatocellular carcinoma. Hepatology. 2009;49(2):460–70.CrossRefPubMed
10.
go back to reference Zhang C, Bai DS, Huang XY, Shi GM, Ke AW, Yang LX, et al. Prognostic significance of Capn4 overexpression in intrahepatic cholangiocarcinoma. PLoS One. 2013;8(1):e54619.PubMedCentralCrossRefPubMed Zhang C, Bai DS, Huang XY, Shi GM, Ke AW, Yang LX, et al. Prognostic significance of Capn4 overexpression in intrahepatic cholangiocarcinoma. PLoS One. 2013;8(1):e54619.PubMedCentralCrossRefPubMed
11.
go back to reference Zhuang Q, Qian X, Cao Y, Fan M, Xu X, He X. Capn4 mRNA level is correlated with tumour progression and clinical outcome in clear cell renal cell carcinoma. J Int Med Res. 2014;42(2):282–91.CrossRefPubMed Zhuang Q, Qian X, Cao Y, Fan M, Xu X, He X. Capn4 mRNA level is correlated with tumour progression and clinical outcome in clear cell renal cell carcinoma. J Int Med Res. 2014;42(2):282–91.CrossRefPubMed
12.
go back to reference Cai JJ, Qi ZX, Hua W, Zhu JJ, Zhang X, Yao Y, et al. Increased expression of Capn4 is associated with the malignancy of human glioma. CNS Neurosci Ther. 2014;20(6):521–7.CrossRefPubMed Cai JJ, Qi ZX, Hua W, Zhu JJ, Zhang X, Yao Y, et al. Increased expression of Capn4 is associated with the malignancy of human glioma. CNS Neurosci Ther. 2014;20(6):521–7.CrossRefPubMed
13.
go back to reference Shimada M, Greer PA, McMahon AP, Bouxsein ML, Schipani E. In vivo targeted deletion of calpain small subunit, Capn4, in cells of the osteoblast lineage impairs cell proliferation, differentiation, and bone formation. J Biol Chem. 2008;283(30):21002–10.PubMedCentralCrossRefPubMed Shimada M, Greer PA, McMahon AP, Bouxsein ML, Schipani E. In vivo targeted deletion of calpain small subunit, Capn4, in cells of the osteoblast lineage impairs cell proliferation, differentiation, and bone formation. J Biol Chem. 2008;283(30):21002–10.PubMedCentralCrossRefPubMed
14.
go back to reference Arthur JS, Elce JS, Hegadorn C, Williams K, Greer PA. Disruption of the murine calpain small subunit gene, Capn4: calpain is essential for embryonic development but not for cell growth and division. Mol Cell Biol. 2000;20(12):4474–81.PubMedCentralCrossRefPubMed Arthur JS, Elce JS, Hegadorn C, Williams K, Greer PA. Disruption of the murine calpain small subunit gene, Capn4: calpain is essential for embryonic development but not for cell growth and division. Mol Cell Biol. 2000;20(12):4474–81.PubMedCentralCrossRefPubMed
15.
go back to reference Gu J, Ding JY, Lu CL, Lin ZW, Chu YW, Zhao GY, et al. Overexpression of CD88 predicts poor prognosis in non-small-cell lung cancer. Lung Cancer. 2013;81(2):259–65.CrossRefPubMed Gu J, Ding JY, Lu CL, Lin ZW, Chu YW, Zhao GY, et al. Overexpression of CD88 predicts poor prognosis in non-small-cell lung cancer. Lung Cancer. 2013;81(2):259–65.CrossRefPubMed
16.
go back to reference Zhao GY, Ding JY, Lu CL, Lin ZW, Guo J. The overexpression of 14-3-3zeta and Hsp27 promotes non-small cell lung cancer progression. Cancer. 2014;120(5):652–63.CrossRefPubMed Zhao GY, Ding JY, Lu CL, Lin ZW, Guo J. The overexpression of 14-3-3zeta and Hsp27 promotes non-small cell lung cancer progression. Cancer. 2014;120(5):652–63.CrossRefPubMed
17.
go back to reference Dai Z, Zhou SL, Zhou ZJ, Bai DS, Xu XY, Fu XT, et al. Capn4 contributes to tumour growth and metastasis of hepatocellular carcinoma by activation of the FAK-Src signalling pathways. J Pathol. 2014;234(3):316–28.CrossRefPubMed Dai Z, Zhou SL, Zhou ZJ, Bai DS, Xu XY, Fu XT, et al. Capn4 contributes to tumour growth and metastasis of hepatocellular carcinoma by activation of the FAK-Src signalling pathways. J Pathol. 2014;234(3):316–28.CrossRefPubMed
18.
go back to reference Zheng PC, Chen X, Zhu HW, Zheng W, Mao LH, Lin C, et al. Capn4 is a marker of poor clinical outcomes and promotes nasopharyngeal carcinoma metastasis via nuclear factor-kappaB-induced matrix metalloproteinase 2 expression. Cancer Sci. 2014;105(6):630–8.CrossRefPubMed Zheng PC, Chen X, Zhu HW, Zheng W, Mao LH, Lin C, et al. Capn4 is a marker of poor clinical outcomes and promotes nasopharyngeal carcinoma metastasis via nuclear factor-kappaB-induced matrix metalloproteinase 2 expression. Cancer Sci. 2014;105(6):630–8.CrossRefPubMed
19.
go back to reference Goldstraw P, Crowley J, Chansky K, Giroux DJ, Groome PA, Rami-Porta R, et al. The IASLC Lung Cancer Staging Project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM Classification of malignant tumours. J Thorac Oncol. 2007;2(8):706–14.CrossRefPubMed Goldstraw P, Crowley J, Chansky K, Giroux DJ, Groome PA, Rami-Porta R, et al. The IASLC Lung Cancer Staging Project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM Classification of malignant tumours. J Thorac Oncol. 2007;2(8):706–14.CrossRefPubMed
20.
go back to reference Dourdin N, Bhatt AK, Dutt P, Greer PA, Arthur JS, Elce JS, et al. Reduced cell migration and disruption of the actin cytoskeleton in calpain-deficient embryonic fibroblasts. J Biol Chem. 2001;276(51):48382–8.PubMed Dourdin N, Bhatt AK, Dutt P, Greer PA, Arthur JS, Elce JS, et al. Reduced cell migration and disruption of the actin cytoskeleton in calpain-deficient embryonic fibroblasts. J Biol Chem. 2001;276(51):48382–8.PubMed
21.
go back to reference Cataldo F, Peche LY, Klaric E, Brancolini C, Myers MP, Demarchi F, et al. CAPNS1 regulates USP1 stability and maintenance of genome integrity. Mol Cell Biol. 2013;33(12):2485–96.PubMedCentralCrossRefPubMed Cataldo F, Peche LY, Klaric E, Brancolini C, Myers MP, Demarchi F, et al. CAPNS1 regulates USP1 stability and maintenance of genome integrity. Mol Cell Biol. 2013;33(12):2485–96.PubMedCentralCrossRefPubMed
22.
go back to reference Duffy MJ, McCarthy K. Matrix metalloproteinases in cancer: prognostic markers and targets for therapy (review). Int J Oncol. 1998;12(6):1343–8.PubMed Duffy MJ, McCarthy K. Matrix metalloproteinases in cancer: prognostic markers and targets for therapy (review). Int J Oncol. 1998;12(6):1343–8.PubMed
23.
go back to reference Yadav L, Puri N, Rastogi V, Satpute P, Ahmad R, Kaur G. Matrix metalloproteinases and cancer-roles in threat and therapy. Asian Pac J Cancer Prev. 2014;15(3):1085–91.CrossRefPubMed Yadav L, Puri N, Rastogi V, Satpute P, Ahmad R, Kaur G. Matrix metalloproteinases and cancer-roles in threat and therapy. Asian Pac J Cancer Prev. 2014;15(3):1085–91.CrossRefPubMed
24.
go back to reference Qian Q, Wang Q, Zhan P, Peng L, Wei SZ, Shi Y, et al. The role of matrix metalloproteinase 2 on the survival of patients with non-small cell lung cancer: a systematic review with meta-analysis. Cancer Invest. 2010;28(6):661–9.CrossRefPubMed Qian Q, Wang Q, Zhan P, Peng L, Wei SZ, Shi Y, et al. The role of matrix metalloproteinase 2 on the survival of patients with non-small cell lung cancer: a systematic review with meta-analysis. Cancer Invest. 2010;28(6):661–9.CrossRefPubMed
25.
go back to reference Thiery JP, Acloque H, Huang RY, Nieto MA. Epithelial-mesenchymal transitions in development and disease. Cell. 2009;139(5):871–90.CrossRefPubMed Thiery JP, Acloque H, Huang RY, Nieto MA. Epithelial-mesenchymal transitions in development and disease. Cell. 2009;139(5):871–90.CrossRefPubMed
26.
go back to reference Ke AW, Shi GM, Zhou J, Huang XY, Shi YH, Ding ZB et al. CD151 amplifies signaling by integrin alpha6beta1 to PI3K and induces the epithelial-mesenchymal transition in HCC cells. Gastroenterology. 2011;140(5):1629–41 e15. Ke AW, Shi GM, Zhou J, Huang XY, Shi YH, Ding ZB et al. CD151 amplifies signaling by integrin alpha6beta1 to PI3K and induces the epithelial-mesenchymal transition in HCC cells. Gastroenterology. 2011;140(5):1629–41 e15.
27.
go back to reference Kim MA, Lee HS, Lee HE, Kim JH, Yang HK, Kim WH. Prognostic importance of epithelial-mesenchymal transition-related protein expression in gastric carcinoma. Histopathology. 2009;54(4):442–51.CrossRefPubMed Kim MA, Lee HS, Lee HE, Kim JH, Yang HK, Kim WH. Prognostic importance of epithelial-mesenchymal transition-related protein expression in gastric carcinoma. Histopathology. 2009;54(4):442–51.CrossRefPubMed
Metadata
Title
Capn4 promotes non-small cell lung cancer progression via upregulation of matrix metalloproteinase 2
Authors
Jie Gu
Feng-kai Xu
Guang-yin Zhao
Chun-lai Lu
Zong-wu Lin
Jian-yong Ding
Di Ge
Publication date
01-03-2015
Publisher
Springer US
Published in
Medical Oncology / Issue 3/2015
Print ISSN: 1357-0560
Electronic ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-015-0500-7

Other articles of this Issue 3/2015

Medical Oncology 3/2015 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.