Enzymatically active cathepsin D sensitizes breast carcinoma
cells to TRAIL

J 2016

Enzymatically active cathepsin D sensitizes breast carcinoma cells to TRAIL

JANČEKOVÁ, Blanka, Eva ONDROUŠKOVÁ, Lucia KNOPFOVÁ, Jan ŠMARDA, Petr BENEŠ et. al.

Základní údaje

Originální název

Enzymatically active cathepsin D sensitizes breast carcinoma cells to TRAIL

Autoři

JANČEKOVÁ, Blanka (203 Česká republika, domácí), Eva ONDROUŠKOVÁ (203 Česká republika, domácí), Lucia KNOPFOVÁ (203 Česká republika, domácí), Jan ŠMARDA (203 Česká republika, domácí) a Petr BENEŠ (203 Česká republika, garant, domácí)

Vydání

Tumor Biology, Springer Netherlands, 2016, 1010-4283

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10601 Cell biology

Stát vydavatele

Nizozemské království

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 3.650

Kód RIV

RIV/00216224:14310/16:00088856

Organizační jednotka

Přírodovědecká fakulta

DOI

http://dx.doi.org/10.1007/s13277-016-4958-5

UT WoS

000382672900068

Klíčová slova česky

Apoptóza; Bcl-2; rakovina prsu; kaspázy; katepsin D; TRAIL

Klíčová slova anglicky

Apoptosis; Bcl-2; Breast cancer; Caspases; Cathepsin D; TRAIL

Štítky

AKR

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 19. 2. 2018 10:00, doc. Mgr. Petr Beneš, Ph.D.

Anotace

V originále

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 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.

Návaznosti

EE2.3.20.0183, projekt VaV

Název: Centrum experimentální biomedicíny

NT13441, projekt VaV

Název: Exprese proteinů rodiny Myb v adenokarcinomech tlustého střeva a vztah k jejich metastatickému potenciálu

Citovat

JANČEKOVÁ, Blanka, Eva ONDROUŠKOVÁ, Lucia KNOPFOVÁ, Jan ŠMARDA a Petr BENEŠ. Enzymatically active cathepsin D sensitizes breast carcinoma cells to TRAIL. Tumor Biology. Springer Netherlands, 2016, roč. 37, č. 8, s. 10685-10696. ISSN 1010-4283. Dostupné z: https://dx.doi.org/10.1007/s13277-016-4958-5.

@article{1344975,
   author = {Jančeková, Blanka and Ondroušková, Eva and Knopfová, Lucia and Šmarda, Jan and Beneš, Petr},
   article_number = {8},
   doi = {http://dx.doi.org/10.1007/s13277-016-4958-5},
   keywords = {Apoptosis; Bcl-2; Breast cancer; Caspases; Cathepsin D; TRAIL},
   language = {eng},
   issn = {1010-4283},
   journal = {Tumor Biology},
   title = {Enzymatically active cathepsin D sensitizes breast carcinoma cells to TRAIL},
   url = {http://link.springer.com/article/10.1007%2Fs13277-016-4958-5},
   volume = {37},
   year = {2016}
}

TY  - JOUR
ID  - 1344975
AU  - Jančeková, Blanka - Ondroušková, Eva - Knopfová, Lucia - Šmarda, Jan - Beneš, Petr
PY  - 2016
TI  - Enzymatically active cathepsin D sensitizes breast carcinoma cells to TRAIL
JF  - Tumor Biology
VL  - 37
IS  - 8
SP  - 10685-10696
EP  - 10685-10696
PB  - Springer Netherlands
SN  - 10104283
KW  - Apoptosis
KW  - Bcl-2
KW  - Breast cancer
KW  - Caspases
KW  - Cathepsin D
KW  - TRAIL
UR  - http://link.springer.com/article/10.1007%2Fs13277-016-4958-5
N2  - 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 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.
ER  -

JANČEKOVÁ, Blanka, Eva ONDROUŠKOVÁ, Lucia KNOPFOVÁ, Jan ŠMARDA a Petr BENEŠ. Enzymatically active cathepsin D sensitizes breast carcinoma cells to TRAIL. \textit{Tumor Biology}. Springer Netherlands, 2016, roč.~37, č.~8, s.~10685-10696. ISSN~1010-4283. Dostupné z: https://dx.doi.org/10.1007/s13277-016-4958-5.

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