Enzymatically active cathepsin D sensitizes breast carcinoma cells to TRAIL
Language English Country United States Media print-electronic
Document type Journal Article
PubMed
26867770
DOI
10.1007/s13277-016-4958-5
PII: 10.1007/s13277-016-4958-5
Knihovny.cz E-resources
- Keywords
- Apoptosis, Bcl-2, Breast cancer, Caspases, Cathepsin D, TRAIL,
- MeSH
- Adenocarcinoma enzymology pathology MeSH
- Enzyme Activation MeSH
- Apoptosis drug effects MeSH
- Drug Resistance, Neoplasm MeSH
- Endosomes metabolism MeSH
- Caspase 8 metabolism MeSH
- Cathepsin D antagonists & inhibitors genetics physiology MeSH
- Hydrogen-Ion Concentration MeSH
- Humans MeSH
- Lysosomes metabolism MeSH
- RNA, Small Interfering genetics MeSH
- Cell Line, Tumor MeSH
- Neoplasm Proteins antagonists & inhibitors genetics physiology MeSH
- Breast Neoplasms enzymology pathology MeSH
- BH3 Interacting Domain Death Agonist Protein metabolism MeSH
- TNF-Related Apoptosis-Inducing Ligand pharmacology MeSH
- Proto-Oncogene Proteins c-bcl-2 metabolism MeSH
- Recombinant Proteins metabolism pharmacology MeSH
- RNA Interference MeSH
- Transfection MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- BID protein, human MeSH Browser
- CASP8 protein, human MeSH Browser
- CTSD protein, human MeSH Browser
- Caspase 8 MeSH
- Cathepsin D MeSH
- RNA, Small Interfering MeSH
- Neoplasm Proteins MeSH
- BH3 Interacting Domain Death Agonist Protein MeSH
- TNF-Related Apoptosis-Inducing Ligand MeSH
- Proto-Oncogene Proteins c-bcl-2 MeSH
- Recombinant Proteins MeSH
- TNFSF10 protein, human MeSH Browser
Cathepsin D (CD), a ubiquitously expressed lysosomal aspartic protease, is upregulated in human breast carcinoma and many other tumor types. CD has been repeatedly reported to act as key mediator of apoptosis induced by various chemotherapeutics. However, there is still controversy over the role of enzymatic/proteolytic versus protein-protein interaction activities of CD in apoptotic signaling. The elucidation of molecular mechanism responsible for the effect of CD in the chemotherapy-induced cell death is crucial for development of an appropriate strategy to target this protease in cancer treatment. Therefore, the objective of this study was to investigate the molecular mechanism behind the CD-mediated regulation of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced cell death. For this purpose, MDA-MB-231 breast carcinoma cells with an increased level of wt CD (CD) or mutant enzymatically inactive CD (ΔCD) were subjected to TRAIL and the frequency of apoptosis was determined. Our results show that CD facilitates the TRAIL-induced apoptosis of MDA-MB-231 breast cancer cells in enzymatic activity-dependent manner. Moreover, the importance of endosomal/lysosomal acidification in this process was documented. Analysis of the potential substrates specifically cleaved by CD during the TRAIL-induced apoptosis confirmed caspase-8 and Bid proteins as the CD targets. Moreover, in search for protein regulators of apoptosis that can be cleaved by CD at physiologically relevant pH, we identified the Bcl-2 protein as a suitable candidate. The modulatory role of CD in cell response to TRAIL was also confirmed in another breast cancer cell line SKBR3. These experiments identified the CD enzymatic activity as a new factor affecting sensitivity of breast cancer cells to TRAIL.
See more in PubMed
Int J Oncol. 2008 Feb;32(2):491-8 PubMed
Mol Cancer. 2012 Mar 23;11:15 PubMed
Int J Cancer. 2002 Feb 20;97(6):775-9 PubMed
Cell Death Differ. 2012 Sep;19(9):1435-45 PubMed
Nat Cell Biol. 2000 Jun;2(6):318-25 PubMed
Oncogene. 2002 Aug 1;21(33):5127-34 PubMed
J Biol Chem. 2012 Jun 15;287(25):21142-51 PubMed
Biochimie. 2010 Nov;92(11):1635-43 PubMed
Arch Pathol Lab Med. 2000 Jul;124(7):966-78 PubMed
J Biochem. 2006 Mar;139(3):583-90 PubMed
Biol Chem. 2012 Dec;393(12):1417-31 PubMed
Cell Death Dis. 2013 Jul 04;4:e702 PubMed
Cancer Res. 1989 Jul 15;49(14 ):3776-82 PubMed
Crit Rev Oncol Hematol. 2008 Oct;68(1):12-28 PubMed
J Cell Biochem. 1996 Jan;60(1):12-7 PubMed
Annu Rev Cell Biol. 1989;5:483-525 PubMed
Cell Death Differ. 2004 May;11(5):550-63 PubMed
J Biol Chem. 2011 Feb 25;286(8):6602-13 PubMed
J Biol Chem. 2007 Sep 28;282(39):28960-70 PubMed
Cancer Lett. 2013 May 28;332(2):265-74 PubMed
EMBO J. 1998 Mar 16;17(6):1675-87 PubMed
Biochim Biophys Acta. 2015 May;1853(5):1182-94 PubMed
Ann Clin Lab Sci. 2012 Summer;42(3):231-42 PubMed
Mol Cell. 1999 Oct;4(4):563-71 PubMed
J Cell Biochem. 2007 Aug 15;101(6):1558-66 PubMed
J Cell Biol. 2005 Jan 31;168(3):489-99 PubMed
FASEB J. 2001 Jul;15(9):1592-4 PubMed
Cell. 1998 Aug 21;94(4):491-501 PubMed
Breast Cancer Res Treat. 1999 May;55(2):137-47 PubMed
Immunity. 2000 Jun;12(6):611-20 PubMed
Cancer Lett. 2012 Oct 28;323(2):208-14 PubMed
Cold Spring Harb Perspect Biol. 2013 Jan 01;5(1):a008755 PubMed
Mol Cancer Ther. 2005 May;4(5):733-42 PubMed
Oncogene. 2002 Aug 29;21(38):5951-5 PubMed
J Biol Chem. 2003 Aug 15;278(33):31401-11 PubMed
J Clin Invest. 1999 Jul;104(2):155-62 PubMed
Curr Med Chem. 2010;17(29):3309-17 PubMed
EMBO J. 1996 Aug 1;15(15):3861-70 PubMed
Nat Med. 1999 Feb;5(2):157-63 PubMed
Apoptosis. 2006 Jul;11(7):1149-59 PubMed
Cell Death Dis. 2013 Feb 21;4:e507 PubMed
Oncogene. 1990 Dec;5(12):1809-14 PubMed
Biol Chem. 2002 Jul-Aug;383(7-8):1237-48 PubMed
Oncogene. 2006 Mar 23;25(13):1967-73 PubMed
Glia. 2003 Aug;43(2):167-74 PubMed
Carcinogenesis. 2008 Oct;29(10 ):1869-77 PubMed
Clin Cancer Res. 2005 Jun 1;11(11):4259-65 PubMed
Cell Death Differ. 2003 Sep;10(9):1090-100 PubMed
Cell Biol Int Rep. 1983 Jun;7(6):405 PubMed
Biochim Biophys Acta. 2008 Oct;1783(10):1755-66 PubMed
Cancer Biol Ther. 2010 Sep 1;10(5):457-66 PubMed
Oncogene. 1998 Apr 30;16(17):2177-83 PubMed
FEBS J. 2013 Jul;280(14):3436-50 PubMed
Biochimie. 2013 Nov;95(11):2010-7 PubMed
Cell Death Differ. 2003 Nov;10(11):1253-9 PubMed
J Biol Chem. 2008 Jul 4;283(27):19140-50 PubMed
Wedelolactone Acts as Proteasome Inhibitor in Breast Cancer Cells
