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Sökning: WFRF:(Ali Amjad) > PIP5K1α is Required...

PIP5K1α is Required for Promoting Tumor Progression in Castration-Resistant Prostate Cancer

Wang, Tianyan (författare)
Umeå universitet,Institutionen för molekylärbiologi (Medicinska fakulteten),Department of Molecular Biology, Umeå University, Umeå, Sweden,Umeå Univ, Dept Mol Biol, Umeå, Sweden.
Sarwar, Martuza (författare)
Umeå universitet,Institutionen för molekylärbiologi (Medicinska fakulteten),Department of Molecular Biology, Umeå University, Umeå, Sweden,Umeå Univ, Dept Mol Biol, Umeå, Sweden.
Whitchurch, Jonathan B. (författare)
School of Pharmacy, University of Nottingham, Nottingham, United Kingdom,Univ Nottingham, Sch Pharm, Nottingham, England.
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Collins, Hilary M. (författare)
School of Pharmacy, University of Nottingham, Nottingham, United Kingdom,Univ Nottingham, Sch Pharm, Nottingham, England.
Green, Tami (författare)
Umeå universitet,Umeå centrum för molekylär medicin (UCMM),Umeå Centre for Molecular Medicine (UCMM), Umeå University, Umeå, Sweden,Umeå Univ, Umeå Ctr Mol Med UCMM, Umeå, Sweden.
Semenas, Julius (författare)
Umeå universitet,Institutionen för molekylärbiologi (Medicinska fakulteten),Department of Molecular Biology, Umeå University, Umeå, Sweden,Umeå Univ, Dept Mol Biol, Umeå, Sweden.
Amjad, Ali (författare)
Umeå universitet,Institutionen för molekylärbiologi (Medicinska fakulteten),Department of Molecular Biology, Umeå University, Umeå, Sweden,Umeå Univ, Dept Mol Biol, Umeå, Sweden.
Roberts, Christopher J. (författare)
School of Pharmacy, University of Nottingham, Nottingham, United Kingdom,Univ Nottingham, Sch Pharm, Nottingham, England.
Morris, Ryan D. (författare)
School of Pharmacy, University of Nottingham, Nottingham, United Kingdom,Univ Nottingham, Sch Pharm, Nottingham, England.
Hubert, Madlen (författare)
Uppsala universitet,Umeå universitet,Institutionen för integrativ medicinsk biologi (IMB),Department of Integrative Medical Biology (IMB), Umeå University, Umeå, Sweden; Department of Pharmacy, Uppsala University, Uppsala, Sweden,Institutionen för farmaci,Umeå Univ, Dept ofIntegrat Med Biol IMB, Umeå, Sweden.
Chen, Sa, 1967- (författare)
Umeå universitet,Patologi,Department of Medical Biosciences, Umeå University, Umeå, Sweden,Umeå Univ, Dept Med Biosci, Umeå, Sweden.
El-Schich, Zahra (författare)
Malmö universitet,Institutionen för biomedicinsk vetenskap (BMV),Malmö Univ, Dept Biomed Sci, Malmö, Sweden.
Wingren, Anette G (författare)
Malmö universitet,Institutionen för biomedicinsk vetenskap (BMV),Malmö Univ, Dept Biomed Sci, Malmö, Sweden.
Grundström, Thomas (författare)
Umeå universitet,Institutionen för molekylärbiologi (Medicinska fakulteten),Department of Molecular Biology, Umeå University, Umeå, Sweden,Umeå Univ, Dept Mol Biol, Umeå, Sweden.
Lundmark, Richard (författare)
Umeå universitet,Institutionen för integrativ medicinsk biologi (IMB),Department of Integrative Medical Biology (IMB), Umeå University, Umeå, Sweden,Umeå Univ, Dept ofIntegrat Med Biol IMB, Umeå, Sweden.
Mongan, Nigel P. (författare)
School of Veterinary Medicine and Science, University of Nottingham, Nottingham, United Kingdom; Department of Pharmacology, Weill Cornell Medicine, New York, NY, United States,Univ Nottingham, Sch Vet Med & Sci, Nottingham, England.;Dept Pharmacol, Weill Cornell Med, New York, NY USA.
Gunhaga, Lena (författare)
Umeå universitet,Umeå centrum för molekylär medicin (UCMM),Umeå Centre for Molecular Medicine (UCMM), Umeå University, Umeå, Sweden,Umeå Univ, Umeå Ctr Mol Med UCMM, Umeå, Sweden.
Heery, David M. (författare)
School of Pharmacy, University of Nottingham, Nottingham, United Kingdom,Univ Nottingham, Sch Pharm, Nottingham, England.
Persson, Jenny L., Professor (författare)
Malmö universitet,Umeå universitet,Institutionen för molekylärbiologi (Medicinska fakulteten),Department of Biomedical Science, Malmö University, Malmö, Sweden; Department of Translational Medicine, Lund University, Clinical Research Centre in Malmö, Malmö, Sweden,Institutionen för biomedicinsk vetenskap (BMV),Department of Molecular Biology, Umeå University, Umeå, Sweden; Department of Translational Medicine, Lund University, Clinical Research Centre in Malmö, Malmö, Sweden,Umeå Univ, Dept Mol Biol, Umeå, Sweden.;Malmö Univ, Dept Biomed Sci, Malmö, Sweden.;Lund Univ, Clin Res Ctr Malmö, Dept Translat Med, Malmö, Sweden.
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 (creator_code:org_t)
2022-03-21
2022
Engelska.
Ingår i: Frontiers in Cell and Developmental Biology. - : Frontiers Media S.A.. - 2296-634X. ; 10
Relaterad länk:
https://doi.org/10.3...
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https://urn.kb.se/re...
https://doi.org/10.3...
https://urn.kb.se/re...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • PIP5K1α has emerged as a promising drug target for the treatment of castration-resistant prostate cancer (CRPC), as it acts upstream of the PI3K/AKT signaling pathway to promote prostate cancer (PCa) growth, survival and invasion. However, little is known of the molecular actions of PIP5K1α in this process. Here, we show that siRNA-mediated knockdown of PIP5K1α and blockade of PIP5K1α action using its small molecule inhibitor ISA-2011B suppress growth and invasion of CRPC cells. We demonstrate that targeted deletion of the N-terminal domain of PIP5K1α in CRPC cells results in reduced growth and migratory ability of cancer cells. Further, the xenograft tumors lacking the N-terminal domain of PIP5K1α exhibited reduced tumor growth and aggressiveness in xenograft mice as compared to that of controls. The N-terminal domain of PIP5K1α is required for regulation of mRNA expression and protein stability of PIP5K1α. This suggests that the expression and oncogenic activity of PIP5K1α are in part dependent on its N-terminal domain. We further show that PIP5K1α acts as an upstream regulator of the androgen receptor (AR) and AR target genes including CDK1 and MMP9 that are key factors promoting growth, survival and invasion of PCa cells. ISA-2011B exhibited a significant inhibitory effect on AR target genes including CDK1 and MMP9 in CRPC cells with wild-type PIP5K1α and in CRPC cells lacking the N-terminal domain of PIP5K1α. These results indicate that the growth of PIP5K1α-dependent tumors is in part dependent on the integrity of the N-terminal sequence of this kinase. Our study identifies a novel functional mechanism involving PIP5K1α, confirming that PIP5K1α is an intriguing target for cancer treatment, especially for treatment of CRPC.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

Nyckelord

androgen receptor (AR)
castration-resistant prostate cancer (CRPC)
cyclin-dependent kinase (CDK)
matrix metalloproteinases 9 (MMP9) PIP5K1α
phosphatidylinositol 4-phosphate 5 kinase (PIP5K1α)
targeted therapy
Oncology
onkologi

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