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Cancers
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Nonlethal Functions of Caspases in Tumors
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Nonlethal Functions of Caspases in Tumors

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Molecular Cancer Biology".

Deadline for manuscript submissions: closed (11 March 2024) | Viewed by 3674

Special Issue Editor

Prof. Dr. Dwayne Stupack

E-Mail Website
Guest Editor
Department of Reproductive Medicine, School of Medicine and Moores Cancer Center, University of California San Diego, La Jolla, CA 92093, USA
Interests: nonapoptotic functions of caspases; cytokine regulation; cytoskeletal dynamics; cell endosomal trafficking, secretion; cell-cell interaction

Special Issue Information

Dear Colleagues,

Apoptosis is an ancient form of programmed cell death (PCD) that is mediated by a conserved group of proteases, the caspases. The canonical role of caspases in mediating cell death is important during development and for tumor suppression. These critical processes have suggested programmed cell death to be the major role of these proteins. Nonetheless, from an evolutionary perspective, caspases predate apoptosis, suggesting that they may once have, and may still, act in other roles in the cell. Although these roles have been termed “noncanonical,” such roles may actually represent the bulk of day-to-day function by caspases, with lethal function representing only the final punctuation of caspase activity.

We are pleased to invite you to contribute to this Special Issue, which is envisioned to contain original research articles, reviews and perspectives. This collection will focus on the day-to-day functions of caspases, and the way in which tumor progression may be aided by these nonlethal functions (NLF) of caspases.

I look forward to receiving your contributions.

Prof. Dr. Dwayne Stupack
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 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. 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

  • caspase
  • nonlethal
  • metastasis
  • cancer
  • apoptosis
  • tumor invasion
  • cytokine
  • signaling

Published Papers (2 papers)

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Research

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21 pages, 6856 KiB  
Article
Synergistic Sensitization of High-Grade Serous Ovarian Cancer Cells Lacking Caspase-8 Expression to Chemotherapeutics Using Combinations of Small-Molecule BRD4 and CDK9 Inhibitors
by Khayal Gasimli, Monika Raab, Ranadip Mandal, Andrea Krämer, Samuel Peña-Llopis, Morva Tahmasbi Rad, Sven Becker, Klaus Strebhardt and Mourad Sanhaji
Cancers 2024, 16(1), 107; https://doi.org/10.3390/cancers16010107 - 24 Dec 2023
Viewed by 1696
Abstract
Ovarian cancer is one of the most lethal gynecological cancers worldwide, with approximately 70% of cases diagnosed in advanced stages. This late diagnosis results from the absence of early warning symptoms and is associated with an unfavorable prognosis. A standard treatment entails a [...] Read more.
Ovarian cancer is one of the most lethal gynecological cancers worldwide, with approximately 70% of cases diagnosed in advanced stages. This late diagnosis results from the absence of early warning symptoms and is associated with an unfavorable prognosis. A standard treatment entails a combination of primary chemotherapy with platinum and taxane agents. Tumor recurrence following first-line chemotherapy with Carboplatin and Paclitaxel is detected in 80% of advanced ovarian cancer patients, with disease relapse occurring within 2 years of initial treatment. Platinum-resistant ovarian cancer is one of the biggest challenges in treating patients. Second-line treatments involve PARP or VEGF inhibitors. Identifying novel biomarkers and resistance mechanisms is critical to overcoming resistance, developing newer treatment strategies, and improving patient survival. In this study, we have determined that low Caspase-8 expression in ovarian cancer patients leads to poor prognosis. High-Grade Serous Ovarian Cancer (HGSOC) cells lacking Caspase-8 expression showed an altered composition of the RNA Polymerase II-containing transcriptional elongation complex leading to increased transcriptional activity. Caspase-8 knockout cells display increased BRD4 expression and CDK9 activity and reduced sensitivities to Carboplatin and Paclitaxel. Based on our work, we are proposing three potential therapeutic approaches to treat advanced ovarian cancer patients who exhibit low Caspase-8 expression and resistance to Carboplatin and/or Paclitaxel—combinations of (1) Carboplatin with small-molecule BRD4 inhibitors; (2) Paclitaxel with small-molecule BRD4 inhibitors, and (3) small-molecule BRD4 and CDK9 inhibitors. In addition, we are also proposing two predictive markers of chemoresistance—BRD4 and pCDK9. Full article
(This article belongs to the Special Issue Nonlethal Functions of Caspases in Tumors)
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Review

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15 pages, 861 KiB  
Review
Caspase-8 and Tyrosine Kinases: A Dangerous Liaison in Cancer
by Claudia Contadini, Alessandra Ferri, Claudia Cirotti, Dwayne Stupack and Daniela Barilà
Cancers 2023, 15(13), 3271; https://doi.org/10.3390/cancers15133271 - 21 Jun 2023
Cited by 1 | Viewed by 1469
Abstract
Caspase-8 is a cysteine-aspartic acid protease that has been identified as an initiator caspase that plays an essential role in the extrinsic apoptotic pathway. Evasion of apoptosis is a hallmark of cancer and Caspase-8 expression is silenced in some tumors, consistent with its [...] Read more.
Caspase-8 is a cysteine-aspartic acid protease that has been identified as an initiator caspase that plays an essential role in the extrinsic apoptotic pathway. Evasion of apoptosis is a hallmark of cancer and Caspase-8 expression is silenced in some tumors, consistent with its central role in apoptosis. However, in the past years, several studies reported an increased expression of Caspase-8 levels in many tumors and consistently identified novel “non-canonical” non-apoptotic functions of Caspase-8 that overall promote cancer progression and sustain therapy resistance. These reports point to the ability of cancer cells to rewire Caspase-8 function in cancer and raise the question of which are the signaling pathways aberrantly activated in cancer that may contribute to the hijack of Caspase-8 activity. In this regard, tyrosine kinases are among the first oncogenes ever identified and genomic, transcriptomic and proteomic studies indeed show that they represent a class of signaling molecules constitutively activated in most of the tumors. Here, we aim to review and discuss the role of Caspase-8 in cancer and its interplay with Src and other tyrosine kinases. Full article
(This article belongs to the Special Issue Nonlethal Functions of Caspases in Tumors)
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