@article{8f4c8bf3a01343dfbaa1a2ac86972231,
title = "PIM1 kinase promotes gallbladder cancer cell proliferation via inhibition of proline-rich Akt substrate of 40 kDa (PRAS40)",
abstract = "Gallbladder cancer (GBC) is a rare malignancy, associated with poor disease prognosis with a 5-year survival of only 20%. This has been attributed to late presentation of the disease, lack of early diagnostic markers and limited efficacy of therapeutic interventions. Elucidation of molecular events in GBC can contribute to better management of the disease by aiding in the identification of therapeutic targets. To identify aberrantly activated signaling events in GBC, tandem mass tag-based quantitative phosphoproteomic analysis of five GBC cell lines was carried out. Proline-rich Akt substrate 40 kDa (PRAS40) was one of the proteins found to be hyperphosphorylated in all the invasive GBC cell lines. Tissue microarray-based immunohistochemical labeling of phospho-PRAS40 (T246) revealed moderate to strong staining in 77% of the primary gallbladder adenocarcinoma cases. Regulation of PRAS40 activity by inhibiting its upstream kinase PIM1 resulted in a significant decrease in cell proliferation, colony forming and invasive ability of GBC cells. Our results support the role of PRAS40 phosphorylation in GBC cell survival and aggressiveness. This study also elucidates phospho-PRAS40 as a clinical marker in GBC and the role of PIM1 as a therapeutic target in GBC.",
keywords = "Cell survival, Gastrointestinal cancer, Phosphoproteomics, SGI-1776, Targeted therapy, mTOR signaling",
author = "Tejaswini Subbannayya and Pamela Leal-Rojas and Alex Zhavoronkov and Ozerov, {Ivan V.} and Mikhail Korzinkin and Niraj Babu and Aneesha Radhakrishnan and Sandip Chavan and Remya Raja and Pinto, {Sneha M.} and Patil, {Arun H.} and Barbhuiya, {Mustafa A.} and Prashant Kumar and Rafael Guerrero-Preston and Sanjay Navani and Tiwari, {Pramod K.} and Kumar, {Rekha Vijay} and Prasad, {T. S.Keshava} and Roa, {Juan Carlos} and Akhilesh Pandey and David Sidransky and Harsha Gowda and Evgeny Izumchenko and Aditi Chatterjee",
note = "Funding Information: Acknowledgements We thank the Department of Biotechnology (DBT), Government of India for research support to the Institute of Bioinformatics. IOB is supported by DBT Program Support on Neuroproteomics and infrastructure for proteomic data analysis (BT/01/ COE/08/05). We thank the “Infosys Foundation” for the research support to the Institute of Bioinformatics. This work was supported by the Science and Engineering Research Board, Department of Science and Technology, Government of India grant “miRNAs in chronic tobacco-induced oral cancer (SR/S0/HS-02081/2012)”; NCI{\textquoteright}s Clinical Proteomic Tumor Analysis Consortium initiative (U24CA160036) and FAMRI-funded 072017_YCSA. P.K. Tiwari acknowledges research support from the Indian Council of Medical Research (ICMR), MP Council of Science & Technology (MPCST), Bhopal and Department of Science and Technology, Government of India. Harsha Gowda is a Wellcome Trust/ DBT India Alliance Early Career Fellow. Juan Carlos Roa acknowledges research support from the National Fund for Scientific and Technological Development (FONDECYT 1170893), and Millennium Institute on immunology and immunotherapy (IMII P09/016-F), Government of Chile. Pamela Leal acknowledges research support from the National Fund for Scientific and Technological Development (FONDECYT 1151008), Government of Chile. Niraj Babu is a recipient of Senior Research Fellowship from the Council for Scientific and Industrial Research (CSIR), Government of India. Remya Raja is a recipient of Research Associateship from Department of Biotechnology, Government of India. Sneha M. Pinto is a recipient of DST INSPIRE Faculty award from Department of Science and Technology, Government of India. We thank Dr. S. K. Shankar of National Institute of Mental Health and Neuro Sciences for providing the use microscope facility. Funding Information: We thank the Department of Biotechnology (DBT), Government of India for research support to the Institute of Bioinformatics. IOB is supported by DBT Program Support on Neuroproteomics and infrastructure for proteomic data analysis (BT/01/COE/08/05). We thank the ?Infosys Foundation? for the research support to the Institute of Bioinformatics. This work was supported by the Science and Engineering Research Board, Department of Science and Technology, Government of India grant ?miRNAs in chronic tobacco-induced oral cancer (SR/S0/HS-02081/2012)?; NCI?s Clinical Proteomic Tumor Analysis Consortium initiative (U24CA160036) and FAMRI-funded 072017_YCSA. P.K. Tiwari acknowledges research support from the Indian Council of Medical Research (ICMR), MP Council of Science & Technology (MPCST), Bhopal and Department of Science and Technology, Government of India. Harsha Gowda is a Wellcome Trust/DBT India Alliance Early Career Fellow. Juan Carlos Roa acknowledges research support from the National Fund for Scientific and Technological Development (FONDECYT 1170893), and Millennium Institute on immunology and immunotherapy (IMII P09/016-F), Government of Chile. Pamela Leal acknowledges research support from the National Fund for Scientific and Technological Development (FONDECYT 1151008), Government of Chile. Niraj Babu is a recipient of Senior Research Fellowship from the Council for Scientific and Industrial Research (CSIR), Government of India. Remya Raja is a recipient of Research Associateship from Department of Biotechnology, Government of India. Sneha M. Pinto is a recipient of DST INSPIRE Faculty award from Department of Science and Technology, Government of India. We thank Dr. S. K. Shankar of National Institute of Mental Health and Neuro Sciences for providing the use microscope facility. Publisher Copyright: {\textcopyright} 2019, The International CCN Society.",
year = "2019",
month = jun,
day = "6",
doi = "10.1007/s12079-018-00503-5",
language = "English (US)",
volume = "13",
pages = "163--177",
journal = "Journal of Cell Communication and Signaling",
issn = "1873-9601",
publisher = "Springer Netherlands",
number = "2",
}