Special Issue "CK2 Regulation of Cell Death and Targeting in Cancer Treatment"

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cancer Biology and Therapeutics".

Deadline for manuscript submissions: 15 December 2021.

Special Issue Editors

Prof. Dr. Khalil Ahmed
E-Mail Website
Guest Editor
1. Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA
2. Research Service, Minneapolis VA Health Care System, Minneapolis, MN 55417, USA
Interests: protein kinase CK2 signal mechanisms; therapy targeting
Special Issues, Collections and Topics in MDPI journals
Dr. Janeen Trembley
E-Mail Website
Co-Guest Editor
1. Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA
2. Research Service, Minneapolis VA Health Care System, Minneapolis, MN 55417, USA
Interests: protein kinase CK2; CDK11 signal mechanisms; therapy targeting
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Protein kinases are a significant portion of the genome with diverse roles. Of the large family of protein kinases, CK2 (previously casein kinase 2 or II) has emerged as a „master regulator“ of a wide range of cellular activities in normal as well as disease states. An aspect that has gained much attention is its nearly uniform dysregulation in all cancers studied. Originally, it was believed that the elevation of CK2 was a reflection of its involvement in cell growth and proliferation, as it was high in both normal proliferating cells and cancer cells. However, subsequently, it became clear that CK2 was a potent suppressor of cell death. With the knowledge that CK2 is essential for cell survival and its targeting results in cell death, CK2 emerged as an important target for cancer therapy. Given the significance of the evolving progress in this area of research, a special section of Biomedicines is dedicated to providing a venue for investigators to publish their research.

Prof. Dr. Khalil Ahmed
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2000 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • CK2
  • casein kinase 2
  • apoptosis
  • cell death
  • proliferation
  • therapeutic targeting
  • oncology
  • cancer

Published Papers (3 papers)

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Research

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Article
Targeting of Protein Kinase CK2 in Acute Myeloid Leukemia Cells Using the Clinical-Grade Synthetic-Peptide CIGB-300
Biomedicines 2021, 9(7), 766; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines9070766 - 01 Jul 2021
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Abstract
Protein kinase CK2 has emerged as an attractive therapeutic target in acute myeloid leukemia (AML), an advent that becomes particularly relevant since the treatment of this hematological neoplasia remains challenging. Here we explored for the first time the effect of the clinical-grade peptide-based [...] Read more.
Protein kinase CK2 has emerged as an attractive therapeutic target in acute myeloid leukemia (AML), an advent that becomes particularly relevant since the treatment of this hematological neoplasia remains challenging. Here we explored for the first time the effect of the clinical-grade peptide-based CK2 inhibitor CIGB-300 on AML cells proliferation and viability. CIGB-300 internalization and subcellular distribution were also studied, and the role of B23/nucleophosmin 1 (NPM1), a major target for the peptide in solid tumors, was addressed by knock-down in model cell lines. Finally, pull-down experiments and phosphoproteomic analysis were performed to study CIGB-interacting proteins and identify the array of CK2 substrates differentially modulated after treatment with the peptide. Importantly, CIGB-300 elicited a potent anti-proliferative and proapoptotic effect in AML cells, with more than 80% of peptide transduced cells within three minutes. Unlike solid tumor cells, NPM1 did not appear to be a major target for CIGB-300 in AML cells. However, in vivo pull-down experiments and phosphoproteomic analysis evidenced that CIGB-300 targeted the CK2α catalytic subunit, different ribosomal proteins, and inhibited the phosphorylation of a common CK2 substrates array among both AML backgrounds. Remarkably, our results not only provide cellular and molecular insights unveiling the complexity of the CIGB-300 anti-leukemic effect in AML cells but also reinforce the rationale behind the pharmacologic blockade of protein kinase CK2 for AML-targeted therapy. Full article
(This article belongs to the Special Issue CK2 Regulation of Cell Death and Targeting in Cancer Treatment)
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Article
CX-4945 and siRNA-Mediated Knockdown of CK2 Improves Cisplatin Response in HPV(+) and HPV(−) HNSCC Cell Lines
Biomedicines 2021, 9(5), 571; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines9050571 - 18 May 2021
Cited by 1 | Viewed by 684
Abstract
Head and neck squamous cell carcinoma (HNSCC) can be categorized into human papillomavirus (HPV) positive or negative disease. Elevated protein kinase CK2 level and activity have been historically observed in HNSCC cells. Previous studies on CK2 in HNSCC did not generally include consideration [...] Read more.
Head and neck squamous cell carcinoma (HNSCC) can be categorized into human papillomavirus (HPV) positive or negative disease. Elevated protein kinase CK2 level and activity have been historically observed in HNSCC cells. Previous studies on CK2 in HNSCC did not generally include consideration of HPV(+) and HPV(−) status. Here, we investigated the response of HPV(+) and HPV(−) HNSCC cells to CK2 targeting using CX-4945 or siRNA downregulation combined with cisplatin treatment. HNSCC cell lines were examined for CK2 expression levels and activity and response to CX-4945, with and without cisplatin. CK2 levels and NFκB p65-related activity were high in HPV(+) HNSCC cells relative to HPV(−) HNSCC cells. Treatment with CX-4945 decreased viability and cisplatin IC50 in all cell lines. Targeting of CK2 increased tumor suppressor protein levels for p21 and PDCD4 in most instances. Further study is needed to understand the role of CK2 in HPV(+) and HPV(−) HNSCC and to determine how incorporation of the CK2-targeted inhibitor CX-4945 could improve cisplatin response in HNSCC. Full article
(This article belongs to the Special Issue CK2 Regulation of Cell Death and Targeting in Cancer Treatment)
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Review

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Review
CK2 Regulation: Perspectives in 2021
Biomedicines 2021, 9(10), 1361; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines9101361 - 30 Sep 2021
Viewed by 447
Abstract
The protein kinase CK2 (CK2) family encompasses a small number of acidophilic serine/threonine kinases that phosphorylate substrates involved in numerous biological processes including apoptosis, cell proliferation, and the DNA damage response. CK2 has also been implicated in many human malignancies and other disorders [...] Read more.
The protein kinase CK2 (CK2) family encompasses a small number of acidophilic serine/threonine kinases that phosphorylate substrates involved in numerous biological processes including apoptosis, cell proliferation, and the DNA damage response. CK2 has also been implicated in many human malignancies and other disorders including Alzheimer′s and Parkinson’s diseases, and COVID-19. Interestingly, no single mechanism describes how CK2 is regulated, including activation by external proteins or domains, phosphorylation, or dimerization. Furthermore, the kinase has an elongated activation loop that locks the kinase into an active conformation, leading CK2 to be labelled a constitutively active kinase. This presents an interesting paradox that remains unanswered: how can a constitutively active kinase regulate biological processes that require careful control? Here, we highlight a selection of studies where CK2 activity is regulated at the substrate level, and discuss them based on the regulatory mechanism. Overall, this review describes numerous biological processes where CK2 activity is regulated, highlighting how a constitutively active kinase can still control numerous cellular activities. It is also evident that more research is required to fully elucidate the mechanisms that regulate CK2 and what causes aberrant CK2 signaling in disease. Full article
(This article belongs to the Special Issue CK2 Regulation of Cell Death and Targeting in Cancer Treatment)
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