PMID- 33844560
OWN - NLM
STAT- MEDLINE
DCOM- 20210617
LR  - 20220531
IS  - 1535-3907 (Electronic)
IS  - 1535-3893 (Linking)
VI  - 20
IP  - 5
DP  - 2021 May 7
TI  - Molecular Profiling Associated with Calcium/Calmodulin-Dependent Protein Kinase 
      Kinase 2 (CAMKK2)-Mediated Carcinogenesis in Gastric Cancer.
PG  - 2687-2703
LID - 10.1021/acs.jproteome.1c00008 [doi]
AB  - Gastric cancer is the fifth most common cancer and the third leading cause of 
      cancer-related death worldwide. We showed previously that 
      calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2), a serine-threonine 
      kinase, is highly expressed in gastric cancer and leads to progression. In the 
      present study, we identified the molecular networks involved in CAMKK2-mediated 
      progression of gastric adenocarcinoma. Treatment of gastric cancer cell lines 
      with a CAMKK2 inhibitor, STO-609, resulted in decreased cell migration, invasion, 
      and colony-forming ability and a G1/S-phase arrest. In addition, tandem mass tag 
      (TMT)-based quantitative proteomic analysis resulted in the identification of 
      7609 proteins, of which 219 proteins were found to be overexpressed and 718 
      downregulated (1.5-fold). Our data identified several key downregulated proteins 
      involved in cell division and cell proliferation, which included DNA replication 
      licensing factors, replication factor C, origin recognition complex, replication 
      protein A and GINS, and mesenchymal markers, upon CAMKK2 inhibition. 
      Immunoblotting and immunofluorescence results showed concordance with our mass 
      spectroscopy data. Taken together, our study supports CAMKK2 as a novel 
      therapeutic target in gastric cancer.
FAU - Najar, Mohd Altaf
AU  - Najar MA
AD  - Center for Systems Biology and Molecular Medicine, Yenepoya Research Centre, 
      Yenepoya (Deemed to be University), Mangalore 575018, India.
FAU - Modi, Prashant Kumar
AU  - Modi PK
AD  - Center for Systems Biology and Molecular Medicine, Yenepoya Research Centre, 
      Yenepoya (Deemed to be University), Mangalore 575018, India.
FAU - Ramesh, Poornima
AU  - Ramesh P
AD  - Center for Systems Biology and Molecular Medicine, Yenepoya Research Centre, 
      Yenepoya (Deemed to be University), Mangalore 575018, India.
FAU - Sidransky, David
AU  - Sidransky D
AD  - Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University 
      School of Medicine, Baltimore, Maryland 21231, United States.
FAU - Gowda, Harsha
AU  - Gowda H
AD  - Center for Systems Biology and Molecular Medicine, Yenepoya Research Centre, 
      Yenepoya (Deemed to be University), Mangalore 575018, India.
AD  - Institute of Bioinformatics, International Technology Park, Bangalore, Karnataka 
      560066, India.
AD  - Manipal Academy of Higher Education (MAHE), Manipal 576104, Karnataka, India.
FAU - Prasad, T S Keshava
AU  - Prasad TSK
AD  - Center for Systems Biology and Molecular Medicine, Yenepoya Research Centre, 
      Yenepoya (Deemed to be University), Mangalore 575018, India.
FAU - Chatterjee, Aditi
AU  - Chatterjee A
AUID- ORCID: 0000-0001-8474-5824
AD  - Center for Systems Biology and Molecular Medicine, Yenepoya Research Centre, 
      Yenepoya (Deemed to be University), Mangalore 575018, India.
AD  - Institute of Bioinformatics, International Technology Park, Bangalore, Karnataka 
      560066, India.
AD  - Manipal Academy of Higher Education (MAHE), Manipal 576104, Karnataka, India.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210412
PL  - United States
TA  - J Proteome Res
JT  - Journal of proteome research
JID - 101128775
RN  - EC 2.7.11.17 (CAMKK2 protein, human)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Kinase)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Calcium
MH  - *Calcium-Calmodulin-Dependent Protein Kinase Kinase/genetics
MH  - Carcinogenesis/genetics
MH  - Humans
MH  - Proteomics
MH  - *Stomach Neoplasms/genetics
OTO - NOTNLM
OT  - CAMKK2
OT  - STO-609
OT  - gastric cancer
OT  - mass spectrometry
EDAT- 2021/04/13 06:00
MHDA- 2021/06/22 06:00
CRDT- 2021/04/12 17:10
PHST- 2021/04/13 06:00 [pubmed]
PHST- 2021/06/22 06:00 [medline]
PHST- 2021/04/12 17:10 [entrez]
AID - 10.1021/acs.jproteome.1c00008 [doi]
PST - ppublish
SO  - J Proteome Res. 2021 May 7;20(5):2687-2703. doi: 10.1021/acs.jproteome.1c00008. 
      Epub 2021 Apr 12.