A serine/threonine protein PIM kinase as a biomarker of cancer and a target for anti-tumor therapy

Panchal, Nagesh Kishan; Sabina, Evan Prince

doi:10.1016/j.lfs.2020.117866

Cited by 53 publications

(27 citation statements)

References 84 publications

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“…We have included the secondary and tertiary structures of PIM2 protein ( Figure 2), and the three-dimensional structural representations for the three PIM kinases overlapped to show their structural similarities and differences that have been published to have a more intuitive understanding of PIM2 kinase [7]. Recent research has demonstrated that PIM2 kinase plays an important role in tumorigenesis, especially in multiple myeloma, lymphoma, acute myeloid leukemia, and in some solid cancers.…”

Section: Ivyspringmentioning

confidence: 99%

Protein kinase PIM2: A simple PIM family kinase with complex functions in cancer metabolism and therapeutics

Wang¹,

Xiu²,

Ren³

et al. 2021

J. Cancer

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PIM2 (proviral integration site for Moloney murine leukemia virus 2) kinase plays an important role as an oncogene in multiple cancers, such as leukemia, liver, lung, myeloma, prostate and breast cancers. PIM2 is largely expressed in both leukemia and solid tumors, and it promotes the transcriptional activation of genes involved in cell survival, cell proliferation, and cell-cycle progression. Many tumorigenic signaling molecules have been identified as substrates for PIM2 kinase, and a variety of inhibitors have been developed for its kinase activity, including SMI-4a, SMI-16a, SGI-1776, JP11646 and DHPCC-9. Here, we summarize the signaling pathways involved in PIM2 kinase regulation and PIM2 mechanisms in various neoplastic diseases. We also discuss the current status and future perspectives for the development of PIM2 kinase inhibitors to combat human cancer, and PIM2 will become a therapeutic target in cancers in the future.

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Section: Ivyspringmentioning

confidence: 99%

Protein kinase PIM2: A simple PIM family kinase with complex functions in cancer metabolism and therapeutics

Wang¹,

Xiu²,

Ren³

et al. 2021

J. Cancer

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“…Preclinical trials of such inhibitory compounds in different cancers suggest that they have positive efficacy, and some of them are currently being studied. In their study, they described the molecular mechanism and signalling mechanisms of PIM kinases, as well as matriculation in multiple cancers and a list of commonly used inhibitors [57]. Dengue virus (DENV) infection is a disease that is common to many areas of the world, and its rising incidence places it among the diseases that pose a serious public health danger.…”

Section: Differential Modulation Of Phosphorylationmentioning

confidence: 99%

Importance of Protein Kinase and Its Inhibitor: A Review

Panneerselvam¹,

Kunjiappan²,

Hegde³

et al. 2021

Biochemistry

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Deregulation of a broad range of protein kinases has been linked to the development and growth of cancer cells. Protein kinases are intracellular enzymes that regulate cell growth and proliferation as well as the triggering and regulation of immune responses. Protein kinases are important therapeutic targets in cancer because of their critical role in signalling mechanisms that drive malignant cell characteristics. Intensive efforts in drug research have been made in this area over the last two decades. The current study delves into the catalytic domain of a protein kinase as well as information transfer from the cell’s membrane to internal targets. It also discusses the function of protein kinases in signal transduction and their cellular signalling pathways. Furthermore, it specifically outlines a systematic method to hybrid therapies to solve the issue of protein kinase resistance. The therapeutic use of nitric oxide, as well as other targets such as Phosphoinositide 3-kinases (PI3K), Protein Kinase B (Akt), serine/threonine protein kinase (mTOR), p38 mitogen-activated protein kinases (p38 MAPK), vascular endothelial growth factor receptors (VEGFR), epidermal growth factor receptors (EGFR), and anaplastic lymphoma (ALK) etc., According to the review article, selective therapy has shown high effectiveness in the treatment of advanced cancer, with protein kinase inhibitors being a main focus of the therapy. As a result, the latest review summarized that, the current state of science with the aim of identifying a novel protein kinase inhibitor that may be utilized in the treatment of advanced cancers.

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“…MONA ALSUBAIE 1-3* , SABINE MATOU-NASRI 1,4* , ABDULLAH ALJEDAI 3* , AHMED ALASKAR [4][5][6] , HAMAD AL-EIDI 1 , SARAH A. ALBABTAIN 7 , KHAWLAH E. ALDILAIJAN 7 , MANAL ALSAYEGH 1 and IBRAHIM B. ALABDULKAREEM 1,7 proviral integration of the Moloney murine leukemia virus (PIM-1) serine/threonine kinase, underpinning the critical regulatory role of PIM-1 in the c-MYC-driven BL tumor cell development (2). The PIM-1 serine/threonine kinase is a highly conserved protein.…”

Section: In Vitro Assessment Of the Efficiency Of The Pim-1 Kinase Pharmacological Inhibitor As A Potential Treatment For Burkitt's Lymphmentioning

confidence: 99%

“…PIM-1 has a constitutive kinase activity that critically regulates cell migration, cell cycle, cell proliferation, cell survival and exerts anti-apoptotic activities ( 4 ). Elevated PIM-1 expression predicts a poor outcome in hematological malignancies, including acute myeloid leukemia, B cell chronic lymphocytic leukemia, diffuse large B cell lymphoma and BL ( 5 ). PIM-1-overexpression contributes to tumorigenesis through three pathways, including inhibiting apoptosis (i.e., programmed cell death), stimulating cell proliferation and promoting genomic instability ( 6 ).…”

Section: Introductionmentioning

confidence: 99%

In vitro assessment of the efficiency of the PIM‑1 kinase pharmacological inhibitor as a potential treatment for Burkitt's lymphoma

et al. 2021

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Burkitt's lymphoma is an aggressive form of lymphoma affecting B lymphocytes. It occurs endemically in Africa and sporadically in the rest of the world. Due to the high proliferation rate of this tumor, intensive multi-drug treatment is required; however, the risk of tumor syndrome lysis is high. Overexpression of the proto-oncogene proviral integration of the Moloney murine leukemia virus (PIM-1) kinase is associated with the development of hematological abnormalities, including Burkitt's lymphoma (BL). PIM-1 primarily exerts anti-apoptotic activities through BAD phosphorylation. The aim of the present study was to investigate the in vitro efficiency of a PIM-1 kinase pharmacological inhibitor (PIM1-1) in BL. The impact of PIM1-1 was evaluated in terms of the viability and apoptosis status of the BL B cell lines, Raji and Daudi, compared with K562 leukemia cells, which highly express PIM-1. Cell viability and apoptotic status were assessed with western blotting, and PIM-1 gene expression was assessed with reverse transcription-quantitative PCR. After 48 h of treatment, PIM1-1 inhibited the Daudi, Raji and K562 cell viability with a half-maximal inhibitory concentration corresponding to 10, 20 and 30 µM PIM1-1, respectively. A significant decrease of ERK phosphorylation was detected in PIM1-1-treated Daudi cells, confirming the antiproliferative effect. The addition of 10 µM PIM1-1 significantly decreased the PIM-1 protein and gene expression in Daudi cells. An inhibition of the pro-apoptotic BAD phosphorylation was observed in the Daudi cells treated with 0.1-1 µM PIM1-1 and 10 µM PIM1-1 decreased BAD phosphorylation in the Raji cells. The apoptotic status of both PIM1-1-treated cells lines were confirmed with the detection of cleaved capase-3. However, no change in cell viability and PIM-1 protein expression was observed in the 10 µM PIM1-1-treated K562 cells. In conclusion, the findings indicated that the PIM1-1 pharmacological inhibitor may have therapeutic potential in BL, but with lower efficiency in leukemia.

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A serine/threonine protein PIM kinase as a biomarker of cancer and a target for anti-tumor therapy

Cited by 53 publications

References 84 publications

Protein kinase PIM2: A simple PIM family kinase with complex functions in cancer metabolism and therapeutics

Protein kinase PIM2: A simple PIM family kinase with complex functions in cancer metabolism and therapeutics

Importance of Protein Kinase and Its Inhibitor: A Review

In vitro assessment of the efficiency of the PIM‑1 kinase pharmacological inhibitor as a potential treatment for Burkitt's lymphoma

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