Browsing by Author "Pandey, Akhilesh"

Now showing 1 - 5 of 5
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    Calcium calmodulin dependent kinase kinase 2-a novel therapeutic target for gastric adenocarcinoma
    (2015) Subbannayya, Yashwanth; Syed, Nazia; Barbhuiya, Mustafa A.; Roa Strauch, Juan Carlos Enrique; Marimuthu, Arivusudar; Sahasrabuddhe, Nandini; Pinto, Sneha M.; Manda, Srikanth Srinivas; Renuse, Santosh; Manju, HC; Zameer, Mohammed Abdul Lateef; Sharma, Jyoti; Brait, Mariana; Srikumar, Kotteazeth; Raja, Remya; Vijaya Kumar, M.; Kumar, KV Veerendra; Prasad, TS Keshava; Ramaswamy, Girija; Kumar, Rekha Vijay; Pandey, Akhilesh; Gowda, Harsha; Chatterjee, Aditi
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    Epigenetic reprogramming of cell cycle genes by ACK1 promotes breast cancer resistance to CDK4/6 inhibitor
    (2023) Sawant, Mithila; Wilson, Audrey; Sridaran, Dhivya; Mahajan, Kiran; O'Conor, Christopher J.; Hagemann, Ian S.; Luo, Jingqin; Weimholt, Cody; Li, Tiandao; Roa, Juan Carlos; Pandey, Akhilesh; Wu, Xinyan; Mahajan, Nupam P.
    Hormone receptor-positive, HER2-negative advanced breast cancers exhibit high sensitivity to CDK4/6 inhibitors such as palbociclib. However, most patients inevitably develop resistance, thus identification of new actionable therapeutic targets to overcome the recurrent disease is an urgent need. Immunohistochemical studies of tissue microarray revealed increased activation of non-receptor tyrosine kinase, ACK1 (also known as TNK2) in most of the breast cancer subtypes, independent of their hormone receptor status. Chromatin immunoprecipitation studies demonstrated that the nuclear target of activated ACK1, pY88-H4 epigenetic marks, were deposited at cell cycle genes, CCNB1, CCNB2 and CDC20, which in turn initiated their efficient transcription. Pharmacological inhibition of ACK1 using its inhibitor, (R)-9b dampened CCNB1, CCNB2 and CDC20 expression, caused G2/M arrest, culminating in regression of palbociclib-resistant breast tumor growth. Further, (R)-9b suppressed expression of CXCR4 receptor, which resulted in significant impairment of metastasis of breast cancer cells to lung. Overall, our pre-clinical data identifies activated ACK1 as an oncogene that epigenetically controls the cell cycle genes governing the G2/M transition in breast cancer cells. ACK1 inhibitor, (R)-9b could be a novel therapeutic option for the breast cancer patients that have developed resistance to CDK4/6 inhibitors.
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    PIM1 kinase promotes gallbladder cancer cell proliferation via inhibition of proline-rich Akt substrate of 40kDa (PRAS40)
    (2019) 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
    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 40kDa (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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    Quantitative phosphoproteomic analysis of IL-33-mediated signaling
    (2015) Pinto, Sneha M.; Sekhar Nirujogi, Raja; Leal Rojas, Pamela; Patil, Arun H.; Manda, Srikanth S.; Subbannayya, Yashwanth; Roa Strauch, Juan Carlos Enrique; Chatterjee, Aditi; Keshava Prasad, T. S.; Pandey, Akhilesh
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    Small molecule inhibitor screening identifified HSP90 inhibitor 17-AAG as potential therapeutic agent for gallbladder cancer
    (2017) Weber, Helga; Valbuena Mora, José Rafael; Barbhuiya, Mustafa A.; Stein, Stefan; Kunkel, Hana; García Muñoz, Patricia; Bizama, Carolina; Riquelme, Ismael; Espinoza, Jaime A.; Kurtz, Stephen E.; Tyner, Jeffrey W.; Calderon, Juan Francisco; Corvalán R., Alejandro; Grez, Manuel; Pandey, Akhilesh; Leal Rojas, Pamela; Roa Strauch, Juan Carlos Enrique