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Cancers
Special Issues
AGC Kinases and Cancer
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AGC Kinases and Cancer

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 20494

Special Issue Editor

Prof. Dr. Alakananda Basu

E-Mail Website
Guest Editor
Department of Microbiology, Immunology & Genetics, University of North Texas Health Science Center, Fort Worth, TX, USA
Interests: signal transduction; Akt; protein kinase C; mechanistic target of rapamycin/S6 kinase; apoptosis; autophagy; senescence; breast cancer
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

AGC kinases are a group of related Ser/Thr protein kinases that acquired the acronym because of the structural similarities with protein kinase A, protein kinase G and protein kinase C at their catalytic domains. There are at least sixty members in the AGC kinase family, including Akt, 3-phosphoinositide-dependent kinase 1 (PDK1), protein kinase C (PKC), S6 kinase (S6K), serum- and glucocorticoid-induced protein kinase (SGK) and Rho-associated coiled-coil containing kinase (ROCK). AGC kinases play important roles in signal transduction and cell regulation. An aberration in several members of the AGC kinase family has been associated with cancer. Many of these AGC kinases exist as several different isoforms that exhibit distinct functions. Proper targeting of AGC kinases for cancer therapy requires a thorough understanding of the structure, function and regulation of different isoforms of a particular AGC kinase and the molecular mechanisms by which they contribute to cancer.  This Special Issue focuses on the involvement of AGC kinases, especially the function of individual isoforms of a particular AGC kinase, in cancer and as potential targets for cancer therapy.

Prof. Dr. Alakananda Basu
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 submissions that pass pre-check are 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 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. Cancers is an international peer-reviewed open access semimonthly 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 2900 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

  • Akt/PKB
  • PDK1
  • PKC
  • RSK
  • S6K
  • SGK
  • ROCK

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Published Papers (4 papers)

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Research

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11 pages, 1043 KiB  
Article
Discovery of a Potent and Highly Isoform-Selective Inhibitor of the Neglected Ribosomal Protein S6 Kinase Beta 2 (S6K2)
by Stefan Gerstenecker, Lisa Haarer, Martin Schröder, Mark Kudolo, Martin P. Schwalm, Valentin Wydra, Ricardo A. M. Serafim, Apirat Chaikuad, Stefan Knapp, Stefan Laufer and Matthias Gehringer
Cancers 2021, 13(20), 5133; https://doi.org/10.3390/cancers13205133 - 13 Oct 2021
Cited by 13 | Viewed by 4022
Abstract
The ribosomal protein S6 kinase beta 2 (S6K2) is thought to play an important role in malignant cell proliferation, but is understudied compared to its closely related homolog S6 kinase beta 1 (S6K1). To better understand the biological function of S6K2, chemical probes [...] Read more.
The ribosomal protein S6 kinase beta 2 (S6K2) is thought to play an important role in malignant cell proliferation, but is understudied compared to its closely related homolog S6 kinase beta 1 (S6K1). To better understand the biological function of S6K2, chemical probes are needed, but the high similarity between S6K2 and S6K1 makes it challenging to selectively address S6K2 with small molecules. We were able to design the first potent and highly isoform-specific S6K2 inhibitor from a known S6K1-selective inhibitor, which was merged with a covalent inhibitor engaging a cysteine located in the hinge region in the fibroblast growth factor receptor kinase (FGFR) 4 via a nucleophilic aromatic substitution (SNAr) reaction. The title compound shows a high selectivity over kinases with an equivalently positioned cysteine, as well as in a larger kinase panel. A good stability towards glutathione and Nα-acetyl lysine indicates a non-promiscuous reactivity pattern. Thus, the title compound represents an important step towards a high-quality chemical probe to study S6K2-specific signaling. Full article
(This article belongs to the Special Issue AGC Kinases and Cancer)
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Review

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16 pages, 4091 KiB  
Review
Targeting Protein Kinase C for Cancer Therapy
by Sijia He, Qi Li, Qian Huang and Jin Cheng
Cancers 2022, 14(5), 1104; https://doi.org/10.3390/cancers14051104 - 22 Feb 2022
Cited by 34 | Viewed by 5439
Abstract
Protein kinase C (PKC) isoforms, a group of serine-threonine kinases, are important regulators in carcinogenesis. Numerous studies have demonstrated that PKC isoforms exert both positive and negative effects on cancer cell demise. In this review, we systematically summarize the current findings on the [...] Read more.
Protein kinase C (PKC) isoforms, a group of serine-threonine kinases, are important regulators in carcinogenesis. Numerous studies have demonstrated that PKC isoforms exert both positive and negative effects on cancer cell demise. In this review, we systematically summarize the current findings on the architecture, activity regulation and biological functions of PKCs, especially their relationship with anti-cancer therapy-induced cell death. Additionally, we elaborate on current knowledge of the effects of PKCs on tumor metabolism and microenvironment, which have gained increasing attention in oncology-related areas. Furthermore, we underscore the basic experimental and clinical implications of PKCs as a target for cancer therapy to evaluate their therapeutic benefits and potential applications. Full article
(This article belongs to the Special Issue AGC Kinases and Cancer)
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17 pages, 2880 KiB  
Review
The Landscape of PDK1 in Breast Cancer
by Na Wang, Jianjiang Fu, Zhihua Li, Ningni Jiang, Yanhong Chen and Juan Peng
Cancers 2022, 14(3), 811; https://doi.org/10.3390/cancers14030811 - 5 Feb 2022
Cited by 18 | Viewed by 3732
Abstract
Given that 3-phosphoinositide-dependent kinase 1 (PDK1) plays a crucial role in the malignant biological behaviors of a wide range of cancers, we review the influence of PDK1 in breast cancer (BC). First, we describe the power of PDK1 in cellular behaviors and characterize [...] Read more.
Given that 3-phosphoinositide-dependent kinase 1 (PDK1) plays a crucial role in the malignant biological behaviors of a wide range of cancers, we review the influence of PDK1 in breast cancer (BC). First, we describe the power of PDK1 in cellular behaviors and characterize the interaction networks of PDK1. Then, we establish the roles of PDK1 in carcinogenesis, growth and survival, metastasis, and chemoresistance in BC cells. More importantly, we sort the current preclinical or clinical trials of PDK1-targeted therapy in BC and find that, even though no selective PDK1 inhibitor is currently available for BC therapy, the combination trials of PDK1-targeted therapy and other agents have provided some benefit. Thus, there is increasing anticipation that PDK1-targeted therapy will have its space in future therapeutic approaches related to BC, and we hope the novel approaches of targeted therapy will be conducive to ameliorating the dismal prognosis of BC patients. Full article
(This article belongs to the Special Issue AGC Kinases and Cancer)
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23 pages, 761 KiB  
Review
Akt Isoforms: A Family Affair in Breast Cancer
by Alakananda Basu and Christoffer Briggs Lambring
Cancers 2021, 13(14), 3445; https://doi.org/10.3390/cancers13143445 - 9 Jul 2021
Cited by 35 | Viewed by 6078
Abstract
Akt, also known as protein kinase B (PKB), belongs to the AGC family of protein kinases. It acts downstream of the phosphatidylinositol 3-kinase (PI3K) and regulates diverse cellular processes, including cell proliferation, cell survival, metabolism, tumor growth and metastasis. The PI3K/Akt signaling pathway [...] Read more.
Akt, also known as protein kinase B (PKB), belongs to the AGC family of protein kinases. It acts downstream of the phosphatidylinositol 3-kinase (PI3K) and regulates diverse cellular processes, including cell proliferation, cell survival, metabolism, tumor growth and metastasis. The PI3K/Akt signaling pathway is frequently deregulated in breast cancer and plays an important role in the development and progression of breast cancer. There are three closely related members in the Akt family, namely Akt1(PKBα), Akt2(PKBβ) and Akt3(PKBγ). Although Akt isoforms share similar structures, they exhibit redundant, distinct as well as opposite functions. While the Akt signaling pathway is an important target for cancer therapy, an understanding of the isoform-specific function of Akt is critical to effectively target this pathway. However, our perception regarding how Akt isoforms contribute to the genesis and progression of breast cancer changes as we gain new knowledge. The purpose of this review article is to analyze current literatures on distinct functions of Akt isoforms in breast cancer. Full article
(This article belongs to the Special Issue AGC Kinases and Cancer)
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