Cathepsin D and eukaryotic translation elongation factor 1 as promising markers of cellular senescence

Hae Ok Byun, Na Kyung Han, Hae June Lee, Ki Bum Kim, Young-Gyu Ko, Gyesoon Yoon, Yun Sil Lee, Seok Il Hong, Jae Seon Lee

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Induction of premature senescence may be a promising strategy for cancer treatment. However, biomarkers for senescent cancer cells are lacking. To identify such biomarkers, we performed comparative proteomic analysis of MCF7human breast cancer cells undergoing cellular senescence in response to ionizing radiation (IR). IR-induced senescence was associated with up-regulation of cathepsin D (CD) and down-regulation of eukaryotic translation elongation factor 1β2 (eEF1B2), as confirmed by Western blot. The other elongation factor, eukaryotic translation elongation factor 1α1 (eEF1A1), was also down-regulated. IR-induced senescence was associated with similar changes of CD and eEF1 (eEF1A1 and eEF1B2) levels in the HCT116 colon cancer cell line and the H460 lung cancer cell line. Up-regulation of CD and down-regulation of eEF1 seemed to be specific to senescence, as they were observed during cellular senescence induced by hydrogen peroxide or anticancer drugs (camptothecin, etoposide, or 50 ng doxorubicin) but not during apoptosis induced by Taxol or 10 Mg doxorubicin or autophagy induced by tamoxifen. The same alterations in CD and eEF1A1 levels were observed during replicative senescence and Ras oncogene-induced senescence. Transient cell cycle arrest did not alter levels of eEF1 or CD. Chemical inhibition of CD (pepstatin A) and small interfering RNA-mediated knockdown of CD and eEF1 revealed that these factors participate in cell proliferation. Finally, the senescence-associated alteration in CD and eEF1 levels observed in cell lines was also observed in IR-exposed xenografted tumors. These findings show that CD and eEF1 are promising markers for the detection of cellular senescence induced by a variety of treatments.

Original languageEnglish
Pages (from-to)4638-4647
Number of pages10
JournalCancer Research
Volume69
Issue number11
DOIs
Publication statusPublished - 2009 Jun 1

Fingerprint

Peptide Elongation Factor 1
Cathepsin D
Cell Aging
Ionizing Radiation
Peptide Elongation Factors
Cell Line
Doxorubicin
Up-Regulation
Down-Regulation
Camptothecin
ras Genes
Autophagy
Etoposide
Tamoxifen
Tumor Biomarkers
Paclitaxel
Cell Cycle Checkpoints
Proteomics
Colonic Neoplasms
Hydrogen Peroxide

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Cathepsin D and eukaryotic translation elongation factor 1 as promising markers of cellular senescence. / Byun, Hae Ok; Han, Na Kyung; Lee, Hae June; Kim, Ki Bum; Ko, Young-Gyu; Yoon, Gyesoon; Lee, Yun Sil; Hong, Seok Il; Lee, Jae Seon.

In: Cancer Research, Vol. 69, No. 11, 01.06.2009, p. 4638-4647.

Research output: Contribution to journalArticle

Byun, HO, Han, NK, Lee, HJ, Kim, KB, Ko, Y-G, Yoon, G, Lee, YS, Hong, SI & Lee, JS 2009, 'Cathepsin D and eukaryotic translation elongation factor 1 as promising markers of cellular senescence', Cancer Research, vol. 69, no. 11, pp. 4638-4647. https://doi.org/10.1158/0008-5472.CAN-08-4042
Byun, Hae Ok ; Han, Na Kyung ; Lee, Hae June ; Kim, Ki Bum ; Ko, Young-Gyu ; Yoon, Gyesoon ; Lee, Yun Sil ; Hong, Seok Il ; Lee, Jae Seon. / Cathepsin D and eukaryotic translation elongation factor 1 as promising markers of cellular senescence. In: Cancer Research. 2009 ; Vol. 69, No. 11. pp. 4638-4647.
@article{254d52a0a39944a3b7887936bcf70f6f,
title = "Cathepsin D and eukaryotic translation elongation factor 1 as promising markers of cellular senescence",
abstract = "Induction of premature senescence may be a promising strategy for cancer treatment. However, biomarkers for senescent cancer cells are lacking. To identify such biomarkers, we performed comparative proteomic analysis of MCF7human breast cancer cells undergoing cellular senescence in response to ionizing radiation (IR). IR-induced senescence was associated with up-regulation of cathepsin D (CD) and down-regulation of eukaryotic translation elongation factor 1β2 (eEF1B2), as confirmed by Western blot. The other elongation factor, eukaryotic translation elongation factor 1α1 (eEF1A1), was also down-regulated. IR-induced senescence was associated with similar changes of CD and eEF1 (eEF1A1 and eEF1B2) levels in the HCT116 colon cancer cell line and the H460 lung cancer cell line. Up-regulation of CD and down-regulation of eEF1 seemed to be specific to senescence, as they were observed during cellular senescence induced by hydrogen peroxide or anticancer drugs (camptothecin, etoposide, or 50 ng doxorubicin) but not during apoptosis induced by Taxol or 10 Mg doxorubicin or autophagy induced by tamoxifen. The same alterations in CD and eEF1A1 levels were observed during replicative senescence and Ras oncogene-induced senescence. Transient cell cycle arrest did not alter levels of eEF1 or CD. Chemical inhibition of CD (pepstatin A) and small interfering RNA-mediated knockdown of CD and eEF1 revealed that these factors participate in cell proliferation. Finally, the senescence-associated alteration in CD and eEF1 levels observed in cell lines was also observed in IR-exposed xenografted tumors. These findings show that CD and eEF1 are promising markers for the detection of cellular senescence induced by a variety of treatments.",
author = "Byun, {Hae Ok} and Han, {Na Kyung} and Lee, {Hae June} and Kim, {Ki Bum} and Young-Gyu Ko and Gyesoon Yoon and Lee, {Yun Sil} and Hong, {Seok Il} and Lee, {Jae Seon}",
year = "2009",
month = "6",
day = "1",
doi = "10.1158/0008-5472.CAN-08-4042",
language = "English",
volume = "69",
pages = "4638--4647",
journal = "Cancer Research",
issn = "0008-5472",
publisher = "American Association for Cancer Research Inc.",
number = "11",

}

TY - JOUR

T1 - Cathepsin D and eukaryotic translation elongation factor 1 as promising markers of cellular senescence

AU - Byun, Hae Ok

AU - Han, Na Kyung

AU - Lee, Hae June

AU - Kim, Ki Bum

AU - Ko, Young-Gyu

AU - Yoon, Gyesoon

AU - Lee, Yun Sil

AU - Hong, Seok Il

AU - Lee, Jae Seon

PY - 2009/6/1

Y1 - 2009/6/1

N2 - Induction of premature senescence may be a promising strategy for cancer treatment. However, biomarkers for senescent cancer cells are lacking. To identify such biomarkers, we performed comparative proteomic analysis of MCF7human breast cancer cells undergoing cellular senescence in response to ionizing radiation (IR). IR-induced senescence was associated with up-regulation of cathepsin D (CD) and down-regulation of eukaryotic translation elongation factor 1β2 (eEF1B2), as confirmed by Western blot. The other elongation factor, eukaryotic translation elongation factor 1α1 (eEF1A1), was also down-regulated. IR-induced senescence was associated with similar changes of CD and eEF1 (eEF1A1 and eEF1B2) levels in the HCT116 colon cancer cell line and the H460 lung cancer cell line. Up-regulation of CD and down-regulation of eEF1 seemed to be specific to senescence, as they were observed during cellular senescence induced by hydrogen peroxide or anticancer drugs (camptothecin, etoposide, or 50 ng doxorubicin) but not during apoptosis induced by Taxol or 10 Mg doxorubicin or autophagy induced by tamoxifen. The same alterations in CD and eEF1A1 levels were observed during replicative senescence and Ras oncogene-induced senescence. Transient cell cycle arrest did not alter levels of eEF1 or CD. Chemical inhibition of CD (pepstatin A) and small interfering RNA-mediated knockdown of CD and eEF1 revealed that these factors participate in cell proliferation. Finally, the senescence-associated alteration in CD and eEF1 levels observed in cell lines was also observed in IR-exposed xenografted tumors. These findings show that CD and eEF1 are promising markers for the detection of cellular senescence induced by a variety of treatments.

AB - Induction of premature senescence may be a promising strategy for cancer treatment. However, biomarkers for senescent cancer cells are lacking. To identify such biomarkers, we performed comparative proteomic analysis of MCF7human breast cancer cells undergoing cellular senescence in response to ionizing radiation (IR). IR-induced senescence was associated with up-regulation of cathepsin D (CD) and down-regulation of eukaryotic translation elongation factor 1β2 (eEF1B2), as confirmed by Western blot. The other elongation factor, eukaryotic translation elongation factor 1α1 (eEF1A1), was also down-regulated. IR-induced senescence was associated with similar changes of CD and eEF1 (eEF1A1 and eEF1B2) levels in the HCT116 colon cancer cell line and the H460 lung cancer cell line. Up-regulation of CD and down-regulation of eEF1 seemed to be specific to senescence, as they were observed during cellular senescence induced by hydrogen peroxide or anticancer drugs (camptothecin, etoposide, or 50 ng doxorubicin) but not during apoptosis induced by Taxol or 10 Mg doxorubicin or autophagy induced by tamoxifen. The same alterations in CD and eEF1A1 levels were observed during replicative senescence and Ras oncogene-induced senescence. Transient cell cycle arrest did not alter levels of eEF1 or CD. Chemical inhibition of CD (pepstatin A) and small interfering RNA-mediated knockdown of CD and eEF1 revealed that these factors participate in cell proliferation. Finally, the senescence-associated alteration in CD and eEF1 levels observed in cell lines was also observed in IR-exposed xenografted tumors. These findings show that CD and eEF1 are promising markers for the detection of cellular senescence induced by a variety of treatments.

UR - http://www.scopus.com/inward/record.url?scp=66349101884&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=66349101884&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-08-4042

DO - 10.1158/0008-5472.CAN-08-4042

M3 - Article

VL - 69

SP - 4638

EP - 4647

JO - Cancer Research

JF - Cancer Research

SN - 0008-5472

IS - 11

ER -