CAMKK2 Promotes Prostate Cancer Independently of AMPK via Increased Lipogenesis

Cancer Research
Lucy PenfoldDavid Carling

Abstract

: New targets are required for treating prostate cancer, particularly castrate-resistant disease. Previous studies reported that calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) expression is increased in human prostate cancer. Here, we show that Camkk2 deletion or pharmacologic inhibition protects against prostate cancer development in a preclinical mouse model that lacks expression of prostate-specific Pten. In contrast, deletion of AMP-activated protein kinase (Ampk) β1 resulted in earlier onset of adenocarcinoma development. These findings suggest for the first time that Camkk2 and Ampk have opposing effects in prostate cancer progression. Loss of CAMKK2 in vivo or in human prostate cancer cells reduced the expression of two key lipogenic enzymes, acetyl-CoA carboxylase and fatty acid synthase. This reduction was mediated via a posttranscriptional mechanism, potentially involving a decrease in protein translation. Moreover, either deletion of CAMKK2 or activation of AMPK reduced cell growth in human prostate cancer cells by inhibiting de novo lipogenesis. Activation of AMPK in a panel of human prostate cancer cells inhibited cell proliferation, migration, and invasion as well as androgen-receptor signaling. The...Continue Reading

References

Feb 28, 2002·The Journal of Biological Chemistry·Hiroshi TokumitsuRyoji Kobayashi
Jun 6, 2002·Trends in Genetics : TIG·Cory Abate-Shen, Michael M Shen
Sep 11, 2004·Biochemical and Biophysical Research Communications·Xiaoqin XiangZhijun Luo
Sep 14, 2007·The Biochemical Journal·Jenny BainPhilip Cohen
Sep 27, 2008·Neuron·Gary A WaymanThomas R Soderling
Dec 4, 2008·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Michael FöllerFlorian Lang
Apr 18, 2009·Molecular Cancer Therapeutics·Hyeon Ung ParkSean P Collins
Sep 2, 2009·Current Genomics·G N Brooke, C L Bevan
Nov 7, 2009·The Journal of Biological Chemistry·Nicolas DzamkoBruce E Kemp
Oct 1, 2010·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Marc ForetzBenoit Viollet
Dec 3, 2010·The Journal of Pathology·Richard FlavinMassimo Loda
Apr 20, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Taasin SrivastavaThomas R Soderling
May 25, 2012·The FEBS Journal·Claudio R Santos, Almut Schulze
Jun 19, 2012·The Biochemical Journal·David CarlingMatthew J Sanders
Jan 1, 2013·Cell Metabolism·Brandon FaubertRussell G Jones
Apr 9, 2013·Biochimica Et Biophysica Acta·Giorgia ZadraMassimo Loda
Dec 20, 2013·Nature Communications·Bing XiaoSteven J Gamblin
Feb 6, 2014·EMBO Molecular Medicine·Giorgia ZadraMassimo Loda
Jan 13, 2015·Archives of Pharmacal Research·Sang-Min Jeon, Nissim Hay
Apr 8, 2015·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Fumin LinBrian York
Jul 15, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·D Grahame Hardie
Feb 25, 2017·Current Opinion in Cell Biology·David Carling
May 26, 2017·Molecular Oncology·Vanessa P HoudeGregory R Steinberg
Jun 18, 2017·Molecular Cell·Daniel Garcia, Reuben J Shaw
Jun 22, 2017·The Journal of Biological Chemistry·Angela M GocherArthur M Edelman
Nov 15, 2017·Molecular Cancer Research : MCR·Diana Vara-CiruelosD Grahame Hardie
Jan 10, 2018·CA: a Cancer Journal for Clinicians·Rebecca L SiegelAhmedin Jemal

❮ Previous
Next ❯

Citations

Jul 11, 2019·Open Biology·Diana Vara-CiruelosD Grahame Hardie
Mar 4, 2020·Molecular Biology Reports·Alicia BortInés Diaz-Laviada
Jul 8, 2020·International Journal of Molecular Sciences·Boris Y ShorningHelen B Pearson
Aug 28, 2020·Frontiers in Cellular and Infection Microbiology·Diana M Dunn, Joshua Munger
Sep 12, 2020·The Journal of Biological Chemistry·Christopher G LangendorfJohn W Scott
Jan 26, 2021·Cellular Oncology (Dordrecht)·Clara LemosBernard Haendler
Dec 31, 2020·International Journal of Molecular Sciences·Fiona M Russell, David Grahame Hardie
Feb 19, 2021·The Journal of Experimental Medicine·Xueli BianZhimin Lu
Apr 17, 2021·Seminars in Cancer Biology·Che-Chia HsuHui-Kuan Lin
Mar 30, 2019·Journal of Chemical Information and Modeling·Elnaz AledavoodCarolina Estarellas
Nov 3, 2021·Cell Death & Disease·Lorna M StewartEmma Evergren

❮ Previous
Next ❯

Related Concepts

Related Feeds

CRISPR (general)

Clustered regularly interspaced short palindromic repeats (CRISPR) are DNA sequences in the genome that are recognized and cleaved by CRISPR-associated proteins (Cas). CRISPR-Cas system enables the editing of genes to create or correct mutations. Discover the latest research on CRISPR here.

CRISPR for Genome Editing

Genome editing technologies enable the editing of genes to create or correct mutations. Clustered regularly interspaced short palindromic repeats (CRISPR) are DNA sequences in the genome that are recognized and cleaved by CRISPR-associated proteins (Cas). Here is the latest research on the use of CRISPR-Cas system in gene editing.

Cell Migration

Cell migration is involved in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. Here is the latest research.

Anthelmintics

Anthelmintics or antihelminthics are a group of antiparasitic drugs that expel parasitic worms (helminths) and other internal parasites from the body by either stunning or killing them and without causing significant damage to the host. Discover the latest research on anthelmintics here.

Cell Migration in Cancer and Metastasis

Migration of cancer cells into surrounding tissue and the vasculature is an initial step in tumor metastasis. Discover the latest research on cell migration in cancer and metastasis here.