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PIM1 kinase promotes gallbladder cancer cell proliferation via inhibition of proline-rich Akt substrate of 40 kDa (PRAS40).
Subbannayya, Tejaswini; Leal-Rojas, Pamela; Zhavoronkov, Alex; Ozerov, Ivan V; Korzinkin, Mikhail; Babu, Niraj; Radhakrishnan, Aneesha; Chavan, Sandip; Raja, Remya; Pinto, Sneha M; Patil, Arun H; Barbhuiya, Mustafa A; Kumar, Prashant; Guerrero-Preston, Rafael; Navani, Sanjay; Tiwari, Pramod K; Kumar, Rekha Vijay; Prasad, T S Keshava; Roa, Juan Carlos; Pandey, Akhilesh; Sidransky, David; Gowda, Harsha; Izumchenko, Evgeny; Chatterjee, Aditi.
Afiliación
  • Subbannayya T; Institute of Bioinformatics, International Technology Park, Bangalore, Karnataka, 560066, India.
  • Leal-Rojas P; Center of Excellence in Translational Medicine (CEMT) &Scientific and Technological Bioresource Nucleus (BIOREN), Universidad de La Frontera, Temuco, Chile.
  • Zhavoronkov A; McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
  • Ozerov IV; Insilico Medicine, Inc., Emerging Technology Centers, Johns Hopkins University at Eastern, Baltimore, MD, 21218, USA.
  • Korzinkin M; Insilico Medicine, Inc., Emerging Technology Centers, Johns Hopkins University at Eastern, Baltimore, MD, 21218, USA.
  • Babu N; Insilico Medicine, Inc., Emerging Technology Centers, Johns Hopkins University at Eastern, Baltimore, MD, 21218, USA.
  • Radhakrishnan A; Institute of Bioinformatics, International Technology Park, Bangalore, Karnataka, 560066, India.
  • Chavan S; Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India.
  • Raja R; Institute of Bioinformatics, International Technology Park, Bangalore, Karnataka, 560066, India.
  • Pinto SM; Institute of Bioinformatics, International Technology Park, Bangalore, Karnataka, 560066, India.
  • Patil AH; Institute of Bioinformatics, International Technology Park, Bangalore, Karnataka, 560066, India.
  • Barbhuiya MA; Center for Systems Biology and Molecular Medicine, Yenepoya (Deemed to be University), Mangalore, Karnataka, 575018, India.
  • Kumar P; Institute of Bioinformatics, International Technology Park, Bangalore, Karnataka, 560066, India.
  • Guerrero-Preston R; School of Biotechnology, KIIT (Deemed to be University), Bhubaneswar, Odisha, 751024, India.
  • Navani S; Department of Pathology and Laboratory Medicine, Pennsylvania State University College of Medicine, Hershey, PA, USA.
  • Tiwari PK; Institute of Bioinformatics, International Technology Park, Bangalore, Karnataka, 560066, India.
  • Kumar RV; Department of Otolaryngology, Head and Neck Surgery, The Johns Hopkins University School of Medicine, 1550 Orleans Street, CRB II, 5M05C, Baltimore, MD, 21231, USA.
  • Prasad TSK; Lab Surgpath, Mumbai, Maharashtra, 400034, India.
  • Roa JC; Centre for Genomics, Molecular and Human Genetics, Jiwaji University, Gwalior, 474011, India.
  • Pandey A; School of Studies in Zoology, Jiwaji University, Gwalior, 474011, India.
  • Sidransky D; Department of Pathology, Kidwai Memorial Institute of Oncology, Bangalore, Karnataka, 560029, India.
  • Gowda H; Institute of Bioinformatics, International Technology Park, Bangalore, Karnataka, 560066, India.
  • Izumchenko E; Center for Systems Biology and Molecular Medicine, Yenepoya (Deemed to be University), Mangalore, Karnataka, 575018, India.
  • Chatterjee A; NIMHANS-IOB Proteomics and Bioinformatics Laboratory, Neurobiology Research Centre, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, 560029, India.
J Cell Commun Signal ; 13(2): 163-177, 2019 Jun.
Article en En | MEDLINE | ID: mdl-30666556
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: J Cell Commun Signal Año: 2019 Tipo del documento: Article País de afiliación: India Pais de publicación: Países Bajos
Texto completo
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XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: J Cell Commun Signal Año: 2019 Tipo del documento: Article País de afiliación: India Pais de publicación: Países Bajos