LIVIVO - Search results -

Search results

Result 1 - 10 of total 35

Search options

Article ; Online: Rac1 promotes kidney collecting duct repair by mechanically coupling cell morphology to mitotic entry.

Bock, Fabian / Dong, Xinyu / Li, Shensen / Viquez, Olga M / Sha, Eric / Tantengco, Matthew / Hennen, Elizabeth M / Plosa, Erin / Ramezani, Alireza / Brown, Kyle L / Whang, Young Mi / Terker, Andrew S / Arroyo, Juan Pablo / Harrison, David G / Fogo, Agnes / Brakebusch, Cord H / Pozzi, Ambra / Zent, Roy

Science advances

2024 Volume 10, Issue 6, Page(s) eadi7840

Abstract: Prolonged obstruction of the ureter, which leads to injury of the kidney collecting ducts, results in permanent structural damage, while early reversal allows for repair. Cell structure is defined by the actin cytoskeleton, which is dynamically organized ...

Abstract	Prolonged obstruction of the ureter, which leads to injury of the kidney collecting ducts, results in permanent structural damage, while early reversal allows for repair. Cell structure is defined by the actin cytoskeleton, which is dynamically organized by small Rho guanosine triphosphatases (GTPases). In this study, we identified the Rho GTPase, Rac1, as a driver of postobstructive kidney collecting duct repair. After the relief of ureteric obstruction, Rac1 promoted actin cytoskeletal reconstitution, which was required to maintain normal mitotic morphology allowing for successful cell division. Mechanistically, Rac1 restricted excessive actomyosin activity that stabilized the negative mitotic entry kinase Wee1. This mechanism ensured mechanical G
MeSH term(s)	Kidney Tubules, Collecting/metabolism ; rac1 GTP-Binding Protein/metabolism ; Cytoskeleton/metabolism ; Actins/metabolism ; Actin Cytoskeleton/metabolism
Chemical Substances	rac1 GTP-Binding Protein (EC 3.6.5.2) ; Actins
Language	English
Publishing date	2024-02-07
Publishing country	United States
Document type	Journal Article
ZDB-ID	2810933-8
ISSN	2375-2548 ; 2375-2548
ISSN (online)	2375-2548
ISSN	2375-2548
DOI	10.1126/sciadv.adi7840
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Article ; Online: Targeting the Hepatocyte Growth Factor and c-Met Signaling Axis in Bone Metastases.

Whang, Young Mi / Jung, Seung Pil / Kim, Meyoung-Kon / Chang, In Ho / Park, Serk In

International journal of molecular sciences

2019 Volume 20, Issue 2

Abstract: Bone metastasis is the terminal stage disease of prostate, breast, renal, and lung cancers, and currently no therapeutic approach effectively cures or prevents its progression to bone metastasis. One of the hurdles to the development of new drugs for ... ...

Abstract	Bone metastasis is the terminal stage disease of prostate, breast, renal, and lung cancers, and currently no therapeutic approach effectively cures or prevents its progression to bone metastasis. One of the hurdles to the development of new drugs for bone metastasis is the complexity and heterogeneity of the cellular components in the metastatic bone microenvironment. For example, bone cells, including osteoblasts, osteoclasts, and osteocytes, and the bone marrow cells of diverse hematopoietic lineages interact with each other via numerous cytokines and receptors. c-Met tyrosine kinase receptor and its sole ligand hepatocyte growth factor (HGF) are enriched in the bone microenvironment, and their expression correlates with the progression of bone metastasis. However, no drugs or antibodies targeting the c-Met/HGF signaling axis are currently available in bone metastatic patients. This significant discrepancy should be overcome by further investigation of the roles and regulation of c-Met and HGF in the metastatic bone microenvironment. This review paper summarizes the key findings of c-Met and HGF in the development of novel therapeutic approaches for bone metastasis.
MeSH term(s)	Animals ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Bone Neoplasms/drug therapy ; Bone Neoplasms/metabolism ; Bone Neoplasms/pathology ; Bone Neoplasms/secondary ; Disease Progression ; Hepatocyte Growth Factor/metabolism ; Humans ; Molecular Targeted Therapy ; Osteoblasts/drug effects ; Osteoblasts/metabolism ; Osteoclasts/drug effects ; Osteoclasts/metabolism ; Proto-Oncogene Proteins c-met/metabolism ; Signal Transduction/drug effects ; Tumor Microenvironment/drug effects
Chemical Substances	Antineoplastic Agents ; Hepatocyte Growth Factor (67256-21-7) ; MET protein, human (EC 2.7.10.1) ; Proto-Oncogene Proteins c-met (EC 2.7.10.1)
Language	English
Publishing date	2019-01-17
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms20020384
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: MEK inhibition enhances efficacy of bacillus Calmette-Guérin on bladder cancer cells by reducing release of Toll-like receptor 2-activated antimicrobial peptides.

Whang, Young Mi / Jin, Su Bin / Park, Serk In / Chang, In Ho

Oncotarget

2017 Volume 8, Issue 32, Page(s) 53168–53179

Abstract: Bacillus Calmette-Guérin (BCG) is one of the standard treatment options for non-muscle-invasive bladder cancer. The details of the biological defense mechanisms against BCG remain unclear. Here, we investigated whether BCG-induced release of ... ...

Abstract	Bacillus Calmette-Guérin (BCG) is one of the standard treatment options for non-muscle-invasive bladder cancer. The details of the biological defense mechanisms against BCG remain unclear. Here, we investigated whether BCG-induced release of antimicrobial peptides (AMPs; e.g., human β-defensin-2, -3, and cathelicidin) is involved with mitogen-activated protein kinase (MAPK) pathways, and investigated the enhanced anticancer effect of BCG through the down-regulation of Toll-like receptors (TLRs) and MAPK pathways in bladder cancer cells. BCG-infected bladder cancer cells produced AMPs as a defense mechanism against BCG, which were reduced by MEK inhibitors by blocking phosphorylation of extracellular signal-regulated kinase (ERK1/2 or MEK) and c-Jun. MEK inhibitors enhanced inhibition of bladder cancer cell growth by decreased binding of c-Jun, p65 and Pol II to the activated protein-1 promoter. Knockdown of TLR2 and TLR4 reduced ERK phosphorylation. Knockdown of TLR 2 decreased release of AMPs, which was similar to the efficacy of MEK inhibitor on BCG-infected cells. BCG-infected bladder cancer cells were more prone to induction of AMP release following TLR2 activation via ERK and c-Jun pathway mediators. In conclusion, our data suggest that the BCG-induced release of AMPs in bladder cancer cells is a promising molecular target for enhancing the immunotherapeutic efficacy of BCG in bladder cancer patients.
Language	English
Publishing date	2017-08-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	2560162-3
ISSN	1949-2553 ; 1949-2553
ISSN (online)	1949-2553
ISSN	1949-2553
DOI	10.18632/oncotarget.18230
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article: Liposome-Encapsulated Bacillus Calmette-Guérin Cell Wall Skeleton Enhances Antitumor Efficiency for Bladder Cancer In Vitro and In Vivo via Induction of AMP-Activated Protein Kinase.

Whang, Young Mi / Yoon, Da Hyeon / Hwang, Gwang Yong / Yoon, Hoyub / Park, Serk In / Choi, Young Wook / Chang, In Ho

Cancers

2020 Volume 12, Issue 12

Abstract: ... ...

Abstract	The
Language	English
Publishing date	2020-12-08
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers12123679
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Metformin Reduces Thyroid Cancer Tumor Growth in the Metastatic Niche of Bone by Inhibiting Osteoblastic RANKL Productions.

Shin, Hyo Shik / Sun, Hyun Jin / Whang, Young Mi / Park, Young Joo / Park, Do Joon / Cho, Sun Wook

Thyroid : official journal of the American Thyroid Association

2020 Volume 31, Issue 5, Page(s) 760–771

Abstract: Background: ...

Abstract	Background:
MeSH term(s)	Animals ; Bone Marrow/drug effects ; Bone Neoplasms/secondary ; Cell Line, Tumor ; Cell Proliferation ; Culture Media, Conditioned ; Hypoglycemic Agents/pharmacology ; In Vitro Techniques ; Metformin/pharmacology ; Mice ; Osteoblasts/drug effects ; RANK Ligand/drug effects ; RANK Ligand/metabolism ; Thyroid Carcinoma, Anaplastic/secondary ; Thyroid Neoplasms/pathology ; Tumor Microenvironment/drug effects
Chemical Substances	Culture Media, Conditioned ; Hypoglycemic Agents ; RANK Ligand ; Metformin (9100L32L2N)
Language	English
Publishing date	2020-09-15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1086044-7
ISSN	1557-9077 ; 1050-7256
ISSN (online)	1557-9077
ISSN	1050-7256
DOI	10.1089/thy.2019.0851
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 3307: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 106: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article: Enhanced Intracellular Delivery of BCG Cell Wall Skeleton into Bladder Cancer Cells Using Liposomes Functionalized with Folic Acid and Pep-1 Peptide.

Yoon, Ho Yub / Yang, Hee Mang / Kim, Chang Hyun / Goo, Yoon Tae / Hwang, Gwang Yong / Chang, In Ho / Whang, Young Mi / Choi, Young Wook

Pharmaceutics

2019 Volume 11, Issue 12

Abstract: Although bacillus Calmette-Guérin cell wall skeleton (BCG-CWS) might function as a potential substitute for live BCG, its use in the treatment of bladder cancer remains limited owing to issues such as insolubility and micrometer-size following exposure ... ...

Abstract	Although bacillus Calmette-Guérin cell wall skeleton (BCG-CWS) might function as a potential substitute for live BCG, its use in the treatment of bladder cancer remains limited owing to issues such as insolubility and micrometer-size following exposure to an aqueous environment. Thus, to develop a novel nanoparticulate system for efficient BCG-CWS delivery, liposomal encapsulation was carried out using a modified emulsification-solvent evaporation method (targets: Size, <200 nm; encapsulation efficiency, ~60%). Further, the liposomal surface was functionalized with specific ligands, folic acid (FA), and Pep-1 peptide (Pep1), as targeting and cell-penetrating moieties, respectively. Functionalized liposomes greatly increased the intracellular uptake of BCG-CWS in the bladder cancer cell lines, 5637 and MBT2. The immunoactivity was verified through elevated cytokine production and a THP-1 migration assay. In vivo antitumor efficacy revealed that the BCG-CWS-loaded liposomes effectively inhibited tumor growth in mice bearing MBT2 tumors. Dual ligand-functionalized liposome was also superior to single ligand-functionalized liposomes. Immunohistochemistry supported the enhanced antitumor effect of BCG-CWS, with IL-6 production and CD4 infiltration. Thus, we conclude that FA- and Pep1-modified liposomes encapsulating BCG-CWS might be a good candidate for bladder cancer treatment with high target selectivity.
Language	English
Publishing date	2019-12-04
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527217-2
ISSN	1999-4923
ISSN	1999-4923
DOI	10.3390/pharmaceutics11120652
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Structure establishment of three-dimensional (3D) cell culture printing model for bladder cancer.

Kim, Myeong Joo / Chi, Byung Hoon / Yoo, James J / Ju, Young Min / Whang, Young Mi / Chang, In Ho

PloS one

2019 Volume 14, Issue 10, Page(s) e0223689

Abstract: Purpose: Two-dimensional (2D) cell culture is a valuable method for cell-based research but can provide unpredictable, misleading data about in vivo responses. In this study, we created a three-dimensional (3D) cell culture environment to mimic tumor ... ...

Abstract	Purpose: Two-dimensional (2D) cell culture is a valuable method for cell-based research but can provide unpredictable, misleading data about in vivo responses. In this study, we created a three-dimensional (3D) cell culture environment to mimic tumor characteristics and cell-cell interactions to better characterize the tumor formation response to chemotherapy. Materials and methods: We fabricated the 3D cell culture samples using a 3D cell bio printer and the bladder cancer cell line 5637. T24 cells were used for 2D cell culture. Then, rapamycin and Bacillus Calmette-Guérin (BCG) were used to examine their cancer inhibition effects using the two bladder cancer cell lines. Cell-cell interaction was measured by measuring e-cadherin and n-cadherin secreted via the epithelial-mesenchymal transition (EMT). Results: We constructed a 3D cell scaffold using gelatin methacryloyl (GelMA) and compared cell survival in 3D and 2D cell cultures. 3D cell cultures showed higher cancer cell proliferation rates than 2D cell cultures, and the 3D cell culture environment showed higher cell-to-cell interactions through the secretion of E-cadherin and N-cadherin. Assessment of the effects of drugs for bladder cancer such as rapamycin and BCG showed that the effect in the 2D cell culture environment was more exaggerated than that in the 3D cell culture environment. Conclusions: We fabricated 3D scaffolds with bladder cancer cells using a 3D bio printer, and the 3D scaffolds were similar to bladder cancer tissue. This technique can be used to create a cancer cell-like environment for a drug screening platform.
MeSH term(s)	Cell Communication ; Cell Culture Techniques ; Cell Line, Tumor ; Cell Proliferation ; Cell Survival ; Cytokines/metabolism ; Humans ; Printing, Three-Dimensional ; Spheroids, Cellular ; Tumor Cells, Cultured ; Urinary Bladder Neoplasms/pathology
Chemical Substances	Cytokines
Language	English
Publishing date	2019-10-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0223689
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Depletion of NBR1 in urothelial carcinoma cells enhances rapamycin-induced apoptosis through impaired autophagy and mitochondrial dysfunction.

Kim, Myeong Joo / Hwang, Gwang Yong / Cho, Min Ji / Chi, Byung Hoon / Park, Serk In / Chang, In Ho / Whang, Young Mi

Journal of cellular biochemistry

2019 Volume 120, Issue 11, Page(s) 19186–19201

Abstract: Rapamycin is well-recognized in the clinical therapeutic intervention for patients with cancer by specifically targeting mammalian target of rapamycin (mTOR) kinase. Rapamycin regulates general autophagy to clear damaged cells. Previously, we identified ... ...

Abstract	Rapamycin is well-recognized in the clinical therapeutic intervention for patients with cancer by specifically targeting mammalian target of rapamycin (mTOR) kinase. Rapamycin regulates general autophagy to clear damaged cells. Previously, we identified increased expression of messenger RNA levels of NBR1 (the neighbor of BRCA1 gene; autophagy cargo receptor) in human urothelial cancer (URCa) cells, which were not exhibited in response to rapamycin treatment for cell growth inhibition. Autophagy plays an important role in cellular physiology and offers protection against chemotherapeutic agents as an adaptive response required for maintaining cellular energy. Here, we hypothesized that loss of NBR1 sensitizes human URCa cells to growth inhibition induced by rapamycin treatment, leading to interruption of protective autophagic activation. Also, the potential role of mitochondria in regulating autophagy was tested to clarify the mechanism by which rapamycin induces apoptosis in NBR1-knockdown URCa cells. NBR1-knockdown URCa cells exhibited enhanced sensitivity to rapamycin associated with the suppression of autophagosomal elongation and mitochondrial defects. Loss of NBR1 expression altered the cellular responses to rapamycin treatment, resulting in impaired ATP homeostasis and an increase in reactive oxygen species (ROS). Although rapamycin treatment-induced autophagy by adenosine monophosphate-activated protein kinase (AMPK) phosphorylation in NBR1-knockdown cells, it did not process the conjugated form of LC3B-II after activation by unc-51 like autophagy-activating kinase 1 (ULK1). NBR1-knockdown URCa cells exhibited rather profound mitochondrial dysfunctions in response to rapamycin treatment as evidenced by Δψm collapse, ATP depletion, ROS accumulation, and apoptosis activation. Therefore, our findings provide a rationale for rapamycin treatment of NBR1-knockdown human urothelial cancer through the regulation of autophagy and mitochondrial dysfunction by regulating the AMPK/mTOR signaling pathway, indicating that NBR1 can be a potential therapeutic target of human urothelial cancer.
MeSH term(s)	Apoptosis/drug effects ; Apoptosis/genetics ; Autophagy/drug effects ; Autophagy/genetics ; Cell Line, Tumor ; Gene Deletion ; Humans ; Intracellular Signaling Peptides and Proteins/deficiency ; Intracellular Signaling Peptides and Proteins/genetics ; Mitochondria/genetics ; Mitochondria/metabolism ; Mitochondria/pathology ; Neoplasm Proteins/deficiency ; Neoplasm Proteins/metabolism ; Sirolimus/pharmacology ; Urinary Bladder Neoplasms/drug therapy ; Urinary Bladder Neoplasms/genetics ; Urinary Bladder Neoplasms/metabolism ; Urinary Bladder Neoplasms/pathology
Chemical Substances	Intracellular Signaling Peptides and Proteins ; NBR1 protein, human ; Neoplasm Proteins ; Sirolimus (W36ZG6FT64)
Language	English
Publishing date	2019-07-11
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	392402-6
ISSN	1097-4644 ; 0730-2312
ISSN (online)	1097-4644
ISSN	0730-2312
DOI	10.1002/jcb.29248
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 1114: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: The immunotherapeutic effects of recombinant Bacillus Calmette-Guérin resistant to antimicrobial peptides on bladder cancer cells.

Cho, Min-Ji / Kim, Myeong Joo / Kim, Kijeong / Choi, Young Wook / Lee, Sang-Jin / Whang, Young Mi / Chang, In Ho

Biochemical and biophysical research communications

2018 Volume 509, Issue 1, Page(s) 167–174

Abstract: Purpose: Although Mycobacterium bovis Bacillus Calmette-Guérin (BCG) is the most widely used bladder cancer immunotherapy, innate immune responses involving antimicrobial peptides (AMPs) cause BCG failure and unwanted side effects. Here, we generated ... ...

Abstract	Purpose: Although Mycobacterium bovis Bacillus Calmette-Guérin (BCG) is the most widely used bladder cancer immunotherapy, innate immune responses involving antimicrobial peptides (AMPs) cause BCG failure and unwanted side effects. Here, we generated genetically modified BCG strains with improved immunotherapeutic effects by adding genes that confer evasion of AMPs. Materials and methods: We constructed recombinant BCG (rBCG) strains expressing Streptococcal inhibitor of complement (Sic), which confers resistance to human α-defensin-1 and cathelicidin, and d-alanyl carrier protein ligase (dltA), which confers resistance to cationic AMPs. Sic and dltA were separately cloned into the pMV306 plasmid and introduced into BCG via electroporation. Then, the efficacy of the rBCGs was tested in a growth inhibition assay using two bladder cancer cell lines (5637, T24). Results: We confirmed the presence of cDNA segments corresponding to the Sic and dltA genes in total mRNA of the rBCG strains containing Sic (rBCG-Sic) and dltA (rBCG-dltA), and these rBCGs showed higher survival against AMPs. The growth inhibitory effects of rBCGs on bladder cancer cells were significantly enhanced compared to those of the parent BCG, and THP-1 migration also increased. After 8 h of infection, the levels of internalization were higher in rBCG-infected bladder cancer cells than in BCG-infected cells, and cells infected with rBCGs showed increased release of antitumor cytokines, such as IL-6/12, TNF-α, and INF-γ, resulting in inhibition of bacterial killing and immune modulation via antimicrobial peptides. Conclusions: rBCG-Sic and rBCG-dltA can effectively evade BCG-stimulated AMPs, and may be significantly improved immunotherapeutic tools to treat bladder cancer.
MeSH term(s)	Antimicrobial Cationic Peptides/immunology ; BCG Vaccine/genetics ; BCG Vaccine/immunology ; BCG Vaccine/pharmacology ; Cancer Vaccines/genetics ; Cancer Vaccines/immunology ; Cancer Vaccines/pharmacology ; Cell Line, Tumor ; Humans ; Immunity, Innate ; Immunotherapy/methods ; Mycobacterium bovis/genetics ; Mycobacterium bovis/immunology ; Recombinant Proteins/genetics ; Recombinant Proteins/immunology ; Recombinant Proteins/pharmacology ; Urinary Bladder Neoplasms/immunology ; Urinary Bladder Neoplasms/pathology ; Urinary Bladder Neoplasms/therapy ; Vaccines, Synthetic/genetics ; Vaccines, Synthetic/immunology ; Vaccines, Synthetic/pharmacology
Chemical Substances	Antimicrobial Cationic Peptides ; BCG Vaccine ; Cancer Vaccines ; Recombinant Proteins ; Vaccines, Synthetic
Language	English
Publishing date	2018-12-20
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	205723-2
ISSN	1090-2104 ; 0006-291X ; 0006-291X
ISSN (online)	1090-2104 ; 0006-291X
ISSN	0006-291X
DOI	10.1016/j.bbrc.2018.12.097
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 116: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Rapamycin enhances growth inhibition on urothelial carcinoma cells through LKB1 deficiency-mediated mitochondrial dysregulation.

Whang, Young Mi / Kim, Myeong Joo / Cho, Min Ji / Yoon, Hoyub / Choi, Young Wook / Kim, Tae-Hyoung / Chang, In Ho

Journal of cellular physiology

2018 Volume 234, Issue 8, Page(s) 13083–13096

Abstract: Rapamycin, a mammalian target of rapamycin (mTOR) inhibitor, has significant potential for application in the treatment of urothelial carcinoma (URCa) of the bladder. Previous studies have shown that regulation of the AMP-activated serine/threonine ... ...

Abstract	Rapamycin, a mammalian target of rapamycin (mTOR) inhibitor, has significant potential for application in the treatment of urothelial carcinoma (URCa) of the bladder. Previous studies have shown that regulation of the AMP-activated serine/threonine protein kinase (AMPK)-mTOR signaling pathway enhances apoptosis by inducing autophagy or mitophagy in bladder cancer. Alteration of liver kinase B1 (LKB1)-AMPK signaling leads to mitochondrial dysfunction and the accumulation of autophagy-related proteins as a result of mitophagy, resulting in enhanced cell sensitivity to drug treatments. Therefore, we hypothesized that LKB1 deficiency in URCa cells could lead to increased sensitivity to rapamycin by inducing mitochondrial defect-mediated mitophagy. To test this, we established stable LKBI-knockdown URCa cells and analyzed the effects of rapamycin on their growth. Rapamycin enhanced growth inhibition and apoptosis in stable LKB1-knockdown URCa cells and in a xenograft mouse model. In spite of the stable downregulation of LKB1 expression, rapamycin induced AMPK activation in URCa cells, causing loss of the mitochondrial membrane potential, ATP depletion, and ROS accumulation, indicating an alteration of mitochondrial biogenesis. Our findings suggest that the absence of LKB1 can be targeted to induce dysregulated mitochondrial biogenesis by rapamycin treatment in the design of novel therapeutic strategies for bladder cancer.
MeSH term(s)	Animals ; Antineoplastic Agents/pharmacology ; Carcinoma, Transitional Cell/metabolism ; Carcinoma, Transitional Cell/pathology ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Humans ; Mice ; Mice, Nude ; Mitophagy/drug effects ; Mitophagy/physiology ; Protein-Serine-Threonine Kinases/metabolism ; Signal Transduction/drug effects ; Sirolimus/pharmacology ; Urinary Bladder Neoplasms/metabolism ; Urinary Bladder Neoplasms/pathology ; Xenograft Model Antitumor Assays
Chemical Substances	Antineoplastic Agents ; STK11 protein, human (EC 2.7.1.-) ; Protein-Serine-Threonine Kinases (EC 2.7.11.1) ; Sirolimus (W36ZG6FT64)
Language	English
Publishing date	2018-12-13
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3116-1
ISSN	1097-4652 ; 0021-9541
ISSN (online)	1097-4652
ISSN	0021-9541
DOI	10.1002/jcp.27979
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Uc I Zs.212: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

To top

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito