Skip to main content
Top
Published in: Tumor Biology 4/2014

01-04-2014 | Research Article

Truncation of inhibitor of growth family protein 5 effectively induces senescence, but not apoptosis in human tongue squamous cell carcinoma cell line

Authors: Lin Qi, Yang Zhang

Published in: Tumor Biology | Issue 4/2014

Login to get access

Abstract

In these studies, inhibitor of growth protein 5 (ING5) and various fragments of it were overexpressed in the human tongue squamous cell carcinoma cell line, HSC-3. The roles of ING5 in HSC-3 cells were then identified in vitro. Our results indicate that intact ING5 can inhibit proliferation and induce apoptosis in HSC-3 cells. Moreover, two truncated fragments of ING5 (aa 1-184 and aa 107-226) can induce cellular senescence. To analyze the signaling pathway involved, western blotting was performed. In these assays, two truncated fragments of ING5 were found to inhibit the cyclin E and CDK2 expression. These results are consistent with the S phase arrest observed with the overexpression of truncated ING5. However, the mechanisms of ING5-induced cellular senescence remain unclear, and extensive investigations are required in future studies.
Literature
1.
go back to reference He GH, Helbing CC, Wagner MJ, Sensen CW, Riabowol K. Phylogenetic analysis of the ING family of PHD finger proteins. Mol Biol Evol. 2005;22:104–16.PubMedCrossRef He GH, Helbing CC, Wagner MJ, Sensen CW, Riabowol K. Phylogenetic analysis of the ING family of PHD finger proteins. Mol Biol Evol. 2005;22:104–16.PubMedCrossRef
3.
go back to reference Russell M, Berardi P, Gong W, Riabowol K. Grow-ING, Age-ING and Die-ING: ING proteins link cancer, senescence and apoptosis. Exp Cell Res. 2006;312:951–61.PubMedCrossRef Russell M, Berardi P, Gong W, Riabowol K. Grow-ING, Age-ING and Die-ING: ING proteins link cancer, senescence and apoptosis. Exp Cell Res. 2006;312:951–61.PubMedCrossRef
4.
go back to reference Soliman MA, Riabowol K. After a decade of study-ING, a PHD for a versatile family of proteins. Trends Biochem Sci. 2007;32:509–19.PubMedCrossRef Soliman MA, Riabowol K. After a decade of study-ING, a PHD for a versatile family of proteins. Trends Biochem Sci. 2007;32:509–19.PubMedCrossRef
5.
go back to reference Doyon Y, Cayrou C, Ullah M, Landry AJ, Côté V, Selleck W, et al. ING tumor suppressor proteins are critical regulators of chromatin acetylation required for genome expression and perpetuation. Mol Cell. 2006;21:51–64.PubMedCrossRef Doyon Y, Cayrou C, Ullah M, Landry AJ, Côté V, Selleck W, et al. ING tumor suppressor proteins are critical regulators of chromatin acetylation required for genome expression and perpetuation. Mol Cell. 2006;21:51–64.PubMedCrossRef
6.
go back to reference Shiseki M, Nagashima M, Pedeux RM, Kitahama-Shiseki M, Miura K, Okamura S, et al. p29ING4 and p28ING5 bind to p53 and p300, and enhance p53 activity. Cancer Res. 2003;63:2373–8.PubMed Shiseki M, Nagashima M, Pedeux RM, Kitahama-Shiseki M, Miura K, Okamura S, et al. p29ING4 and p28ING5 bind to p53 and p300, and enhance p53 activity. Cancer Res. 2003;63:2373–8.PubMed
7.
go back to reference Cengiz B, Gunduz E, Gunduz M, Beder LB, Tamamura R, Bagci C, et al. Tumor-specific mutation and downregulation of ING5 detected in oral squamous cell carcinoma. Int J Cancer. 2010;127:2088–94.PubMedCrossRef Cengiz B, Gunduz E, Gunduz M, Beder LB, Tamamura R, Bagci C, et al. Tumor-specific mutation and downregulation of ING5 detected in oral squamous cell carcinoma. Int J Cancer. 2010;127:2088–94.PubMedCrossRef
8.
go back to reference Hayflick L, Moorhead PS. The serial cultivation of human diploid cell strains. Exp Cell Res. 1961;25:585–621.PubMedCrossRef Hayflick L, Moorhead PS. The serial cultivation of human diploid cell strains. Exp Cell Res. 1961;25:585–621.PubMedCrossRef
9.
go back to reference Harley CB, Futcher AB, Greider CW. Telomeres shorten during ageing of human fibroblasts. Nature. 1990;345:458–60.PubMedCrossRef Harley CB, Futcher AB, Greider CW. Telomeres shorten during ageing of human fibroblasts. Nature. 1990;345:458–60.PubMedCrossRef
11.
go back to reference Pazolli E, Stewart SA. Senescence: the good the bad and the dysfunctional. Curr Opin Genet Dev. 2008;18:42–7.PubMedCrossRef Pazolli E, Stewart SA. Senescence: the good the bad and the dysfunctional. Curr Opin Genet Dev. 2008;18:42–7.PubMedCrossRef
12.
go back to reference Sun X, Liu B, Wang J, Li J, Ji WY. Inhibition of p21-activated kinase 4 expression suppresses the proliferation of Hep-2 laryngeal carcinoma cells via activation of the ATM/Chk1/2/p53 pathway. Int J Oncol. 2013;42:683–9.PubMed Sun X, Liu B, Wang J, Li J, Ji WY. Inhibition of p21-activated kinase 4 expression suppresses the proliferation of Hep-2 laryngeal carcinoma cells via activation of the ATM/Chk1/2/p53 pathway. Int J Oncol. 2013;42:683–9.PubMed
13.
go back to reference Dimri GP, Lee X, Basile G, Acosta M, Scott G, Roskelley C, et al. A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc Natl Acad Sci U S A. 1995;92:9363–7.PubMedCentralPubMedCrossRef Dimri GP, Lee X, Basile G, Acosta M, Scott G, Roskelley C, et al. A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc Natl Acad Sci U S A. 1995;92:9363–7.PubMedCentralPubMedCrossRef
14.
go back to reference Unoki M, Kumamoto K, Takenoshita S, Harris CC. Reviewing the current classification of inhibitor of growth family proteins. Cancer Sci. 2009;100:1173–9.PubMedCentralPubMedCrossRef Unoki M, Kumamoto K, Takenoshita S, Harris CC. Reviewing the current classification of inhibitor of growth family proteins. Cancer Sci. 2009;100:1173–9.PubMedCentralPubMedCrossRef
16.
go back to reference Garkavtsev I, Riabowol K. Extension of the replicative life span of human diploid fibroblasts by inhibition of the p33ING1 candidate tumor suppressor. Mol Cell Biol. 1997;17:2014–9.PubMedCentralPubMed Garkavtsev I, Riabowol K. Extension of the replicative life span of human diploid fibroblasts by inhibition of the p33ING1 candidate tumor suppressor. Mol Cell Biol. 1997;17:2014–9.PubMedCentralPubMed
17.
go back to reference Schwarze SR, DePrimo SE, Grabert LM, Fu VX, Brooks JD, Jarrard DF. Novel pathways associated with bypassing cellular senescence in human prostate epithelial cells. J Biol Chem. 2002;17:14877–83.CrossRef Schwarze SR, DePrimo SE, Grabert LM, Fu VX, Brooks JD, Jarrard DF. Novel pathways associated with bypassing cellular senescence in human prostate epithelial cells. J Biol Chem. 2002;17:14877–83.CrossRef
18.
go back to reference Kumamoto K, Spillare EA, Fujita K, Horikawa I, Yamashita T, Appella E, et al. Nutlin-3a activates p53 to both down-regulate inhibitor of growth 2 and up-regulate mir-34a, mir-34b, and mir-34c expression, and induce senescence. Cancer Res. 2008;68:3193–203.PubMedCentralPubMedCrossRef Kumamoto K, Spillare EA, Fujita K, Horikawa I, Yamashita T, Appella E, et al. Nutlin-3a activates p53 to both down-regulate inhibitor of growth 2 and up-regulate mir-34a, mir-34b, and mir-34c expression, and induce senescence. Cancer Res. 2008;68:3193–203.PubMedCentralPubMedCrossRef
19.
go back to reference Iglesias-Bartolome R, Patel V, Cotrim A, Leelahavanichkul K, Molinolo AA, Mitchell JB, et al. mTOR inhibition prevents epithelial stem cell senescence and protects from radiation-induced mucositis. Cell Stem Cell. 2012;11:401–14.PubMedCentralPubMedCrossRef Iglesias-Bartolome R, Patel V, Cotrim A, Leelahavanichkul K, Molinolo AA, Mitchell JB, et al. mTOR inhibition prevents epithelial stem cell senescence and protects from radiation-induced mucositis. Cell Stem Cell. 2012;11:401–14.PubMedCentralPubMedCrossRef
20.
go back to reference Rajarajacholan UK, Thalappilly S, Riabowol K. The ING1a tumor suppressor regulates endocytosis to induce cellular senescence via the Rb-E2F pathway. PLoS Biol. 2013;11:e1001502.PubMedCentralPubMedCrossRef Rajarajacholan UK, Thalappilly S, Riabowol K. The ING1a tumor suppressor regulates endocytosis to induce cellular senescence via the Rb-E2F pathway. PLoS Biol. 2013;11:e1001502.PubMedCentralPubMedCrossRef
Metadata
Title
Truncation of inhibitor of growth family protein 5 effectively induces senescence, but not apoptosis in human tongue squamous cell carcinoma cell line
Authors
Lin Qi
Yang Zhang
Publication date
01-04-2014
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 4/2014
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-013-1410-y

Other articles of this Issue 4/2014

Tumor Biology 4/2014 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

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