Cystatin SN neutralizes the inhibitory effect of cystatin C on cathepsin B activity

Cell Death & Disease
J-T KimH G Lee

Abstract

Cystatin SN (CST1) is one of the several salivary cystatins that form tight equimolar complexes with cysteine proteases, such as the cathepsins. High expression of CST1 is correlated with advanced pTNM stage in gastric cancer. However, the functional role of CST1 in tumorigenesis has not been elucidated. In this study, we showed that CST1 was highly expressed in colon tumor tissues, compared with nontumor regions. Increased cell proliferation and invasiveness were observed in HCT116 cell lines stably transfected with CST1 cDNA (HCT116-CST1) but not in CST3-transfected cells. We also demonstrated that CST1-overexpressing cell lines exhibited increased tumor growth as well as metastasis in a xenograft nude mouse model. Interestingly, CST1 interacted with cystatin C (CST3), a potent cathepsin B (CTSB) inhibitor, with a higher affinity than the interaction between CST3 and CTSB in the extracellular space of HCT116 cells. CTSB-mediated cellular invasiveness and proteolytic activities were strongly inhibited by CST3, but in the presence of CST1 CTSB activities recovered significantly. Furthermore, domain mapping of CST1 showed that the disulfide-bonded conformation, or conserved folding, of CST1 is important for its secretion and for...Continue Reading

References

Jan 1, 1992·Critical Reviews in Oral Biology and Medicine : an Official Publication of the American Association of Oral Biologists·L A Bobek, M J Levine
Sep 1, 1990·Scandinavian Journal of Clinical and Laboratory Investigation·D J ButtleM Abrahamson
Feb 17, 1995·Journal of Molecular Biology·J R MartinJ P Waltho
Nov 25, 1997·Journal of Cellular Physiology·G S MerzH M Wisniewski
Sep 14, 1999·Oral Diseases·A BaronJ Featherstone
Oct 3, 1999·International Journal of Cancer. Journal International Du Cancer·S CoulibalyL Mach
Feb 17, 2000·Clinica Chimica Acta; International Journal of Clinical Chemistry·J E KoblinskiB F Sloane
Mar 10, 2000·Biochimica Et Biophysica Acta·J Travis, J Potempa
Jun 8, 2000·Amyloid : the International Journal of Experimental and Clinical Investigation : the Official Journal of the International Society of Amyloidosis·I Olafsson, A Grubb
Apr 11, 2001·Amyloid : the International Journal of Experimental and Clinical Investigation : the Official Journal of the International Society of Amyloidosis·M BjarnadottirA Grubb
Sep 5, 2001·The EMBO Journal·V TurkD Turk
Jul 11, 2002·Biological Chemistry·Natasa SeverTamara T Lah
Mar 18, 2004·Clinica Chimica Acta; International Journal of Clinical Chemistry·Izabela Berdowska
Sep 20, 2005·Proteins·Robert JanowskiMariusz Jaskolski
Sep 23, 2006·Nature Reviews. Cancer·Mona Mostafa Mohamed, Bonnie F Sloane
Oct 20, 2006·Journal of Nanoscience and Nanotechnology·Mateja CegnarJulijana Kristl
Dec 23, 2006·Science·Chava Kimchi-SarfatyMichael M Gottesman
May 26, 2009·Clinica Chimica Acta; International Journal of Clinical Chemistry·Eun Hwa ChoiHee Gu Lee

❮ Previous
Next ❯

Citations

Mar 3, 2004·Biopolymers·Jinfa YingVictor J Hruby
Feb 15, 2003·Journal of the American Society for Mass Spectrometry·Yeu Young YounMyung Soo Kim
Sep 24, 2016·Respiratory Research·Fatemeh MoheimaniDarryl A Knight
May 20, 2017·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Da-Nian DaiWei-Dong Wei
Jul 6, 2017·PLoS Computational Biology·Xiaoping LiuKazuyuki Aihara
Apr 27, 2018·American Journal of Respiratory Cell and Molecular Biology·Yukinori KatoShigeharu Fujieda
Mar 29, 2014·Fukushima Journal of Medical Science·Azusa SuganamiJunko Kimura
Jan 13, 2015·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Jie JiangBin Wu
May 31, 2018·International Journal of Oncology·Jie JiangBin Wu
May 25, 2020·Molecular Cell·Shwu-Yuan WuCheng-Ming Chiang

❮ Previous
Next ❯

Methods Mentioned

BETA
xenograft
fluorescence microscopy
confocal microscopy
PCR

Software Mentioned

Zeiss LSM Image Browser
TP800

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.