TY - JOUR
T1 - Molecular Profiling Associated with Calcium/Calmodulin-Dependent Protein Kinase Kinase 2 (CAMKK2)-Mediated Carcinogenesis in Gastric Cancer
AU - Najar, Mohd Altaf
AU - Modi, Prashant Kumar
AU - Ramesh, Poornima
AU - Sidransky, David
AU - Gowda, Harsha
AU - Prasad, T. S.Keshava
AU - Chatterjee, Aditi
N1 - Funding Information:
We thank Karnataka Biotechnology and Information Technology Services (KBITS), the Government of Karnataka, for the support of the Center for Systems Biology and Molecular Medicine at Yenepoya (Deemed to be University) under the Biotechnology Skill Enhancement Programme in Multiomics Technology (BiSEP GO ITD 02 MDA 2017). M.A.N. is a recipient of a Senior Research Fellowship from the University Grants Commission (UGC), Government of India. P.R. is a recipient of a Senior Research Fellowship from the Indian Council of Medical Research (ICMR), Government of India.
Publisher Copyright:
© 2021 American Chemical Society.
PY - 2021/5/7
Y1 - 2021/5/7
N2 - 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.
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.
KW - CAMKK2
KW - STO-609
KW - gastric cancer
KW - mass spectrometry
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U2 - 10.1021/acs.jproteome.1c00008
DO - 10.1021/acs.jproteome.1c00008
M3 - Article
C2 - 33844560
AN - SCOPUS:85105088256
SN - 1535-3893
VL - 20
SP - 2687
EP - 2703
JO - Journal of proteome research
JF - Journal of proteome research
IS - 5
ER -