Literature DB >> 25756516

Calcium calmodulin dependent kinase kinase 2 - a novel therapeutic target for gastric adenocarcinoma.

Yashwanth Subbannayya1, Nazia Syed, Mustafa A Barbhuiya, Remya Raja, Arivusudar Marimuthu, Nandini Sahasrabuddhe, Sneha M Pinto, Srikanth Srinivas Manda, Santosh Renuse, H C Manju, Mohammed Abdul Lateef Zameer, Jyoti Sharma, Mariana Brait, Kotteazeth Srikumar, Juan Carlos Roa, M Vijaya Kumar, K V Veerendra Kumar, T S Keshava Prasad, Girija Ramaswamy, Rekha Vijay Kumar, Akhilesh Pandey, Harsha Gowda, Aditi Chatterjee.   

Abstract

Gastric cancer is one of the most common gastrointestinal malignancies and is associated with poor prognosis. Exploring alterations in the proteomic landscape of gastric cancer is likely to provide potential biomarkers for early detection and molecules for targeted therapeutic intervention. Using iTRAQ-based quantitative proteomic analysis, we identified 22 proteins that were overexpressed and 17 proteins that were downregulated in gastric tumor tissues as compared to the adjacent normal tissue. Calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) was found to be 7-fold overexpressed in gastric tumor tissues. Immunohistochemical labeling of tumor tissue microarrays for validation of CAMKK2 overexpression revealed that it was indeed overexpressed in 94% (92 of 98) of gastric cancer cases. Silencing of CAMKK2 using siRNA significantly reduced cell proliferation, colony formation and invasion of gastric cancer cells. Our results demonstrate that CAMKK2 signals in gastric cancer through AMPK activation and suggest that CAMKK2 could be a novel therapeutic target in gastric cancer.

Entities:  

Keywords:  LC-MS/MS, Liquid chromatography-tandem mass spectrometry; PSM, Peptide spectrum match; SCX, Strong cation exchange chromatography; iTRAQ, Isobaric tags for relative and absolute quantitation; in vitro labeling; invasion; mass spectrometry; proliferation; siRNA, short interfering RNA; targeted therapy

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Year:  2015        PMID： 25756516      PMCID： PMC4622549          DOI： 10.4161/15384047.2014.972264

Source DB:  PubMed          Journal:  Cancer Biol Ther        ISSN： 1538-4047            Impact factor:   4.742


  52 in total

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Journal:  Proteomics       Date:  2010-09       Impact factor: 3.984

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Journal:  Dig Dis       Date:  2010-11-18       Impact factor: 2.404

9.  Analysis of variabilities of serum proteomic spectra in patients with gastric cancer before and after operation.

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Journal:  Trends Mol Med       Date:  2013-01-14       Impact factor: 11.951
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  27 in total

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2.  Chronic Cigarette Smoke Mediated Global Changes in Lung Mucoepidermoid Cells: A Phosphoproteomic Analysis.

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4.  A complete map of the Calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) signaling pathway.

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Journal:  Cancer Biol Ther       Date:  2016-02-06       Impact factor: 4.742

Review 6.  A spatiotemporal hypothesis for the regulation, role, and targeting of AMPK in prostate cancer.

Authors:  Ayesha S Khan; Daniel E Frigo
Journal:  Nat Rev Urol       Date:  2017-02-01       Impact factor: 14.432

Review 7.  Regulation and role of CAMKK2 in prostate cancer.

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8.  Tyrosine Phosphorylation Profiling Revealed the Signaling Network Characteristics of CAMKK2 in Gastric Adenocarcinoma.

Authors:  Mohd Altaf Najar; Mohammad Arefian; David Sidransky; Harsha Gowda; T S Keshava Prasad; Prashant Kumar Modi; Aditi Chatterjee
Journal:  Front Genet       Date:  2022-05-13       Impact factor: 4.772

Review 9.  Functional characterization of AMP-activated protein kinase signaling in tumorigenesis.

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10.  Identification of differentially expressed serum proteins in gastric adenocarcinoma.

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Journal:  J Proteomics       Date:  2015-05-05       Impact factor: 4.044
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