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Survival Pathways Involved in Resistance to Apoptosis in Cancer

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 March 2020) | Viewed by 27393

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Special Issue Editors

Prof. Dr. Bertrand Liagre

E-Mail Website
Guest Editor

LABC/i/S UR 22722, Faculté de Pharmacie, Université de Limoges, 87000 Limoges, France
Interests: cancer; photodynamic therapy; apoptosis; cyclooxygenase-2
Special Issues, Collections and Topics in MDPI journals

Dr. David Léger

E-Mail Website
Guest Editor

Faculté de Pharmacie, Université de Limoges, F-87025 Limoges, France
Interests: cancer; apoptosis; cyclooxygenase-2; megakaryocytic differentiation; photodynamic therapy

Special Issue Information

Dear Colleagues,

This Special Issue, “Survival Pathways Involved in Resistance to Apoptosis in Cancer”, will cover a selection of recent research topics and current review articles related to the intracellular signaling of resistance to apoptosis in cancer. Up-to-date review articles, commentaries, and experimental papers are all welcome.

Programmed cell death or apoptosis is a natural mechanism by which organisms control the number of cells. It plays an important role in embryonic development and in maintaining cell homeostasis. Deregulation of apoptosis machinery induces resistance to apoptosis. This resistance is characterized by inhibition of cell death triggering or delay in cell death unfolding in response to an apoptotic stimulus. Apoptosis resistance plays an important role in tumor development. Uncontrolled cell proliferation combined with resistance to apoptosis is both necessary and sufficient for tumor progression to a malignant phenotype. Although there are several mechanisms by which cells escape apoptosis, the majority of these lead to an inability for the cell to trigger the intrinsic pathway of apoptosis (called the mitochondrial pathway). Despite numerous studies of the survival pathways in the apoptosis resistance mechanism, the signaling pathways involved have not yet been fully elucidated, and there are disparities regarding their role in this mechanism.

Prof. Bertrand Liagre
Dr. David Léger
Guest Editors

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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

cancer
apoptosis
survival pathways
new treatment
clinical trials

Published Papers (5 papers)

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Research

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22 pages, 3591 KiB

Open AccessArticle

Priming with HDAC Inhibitors Sensitizes Ovarian Cancer Cells to Treatment with Cisplatin and HSP90 Inhibitors

by Ana J. Rodrigues Moita, Jan J. Bandolik, Finn K. Hansen, Thomas Kurz, Alexandra Hamacher and Matthias U. Kassack

Int. J. Mol. Sci. 2020, 21(21), 8300; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21218300 - 05 Nov 2020

Cited by 10 | Viewed by 2777

Abstract

Ovarian cancer is the fifth leading cause of cancer deaths. Chemoresistance, particularly against platinum compounds, contributes to a poor prognosis. Histone deacetylase inhibitors (HDACi) and heat shock protein 90 inhibitors (HSP90i) are known to modulate pathways involved in chemoresistance. This study investigated the effects of HDACi (panobinostat, LMK235) and HSP90i (luminespib, HSP990) on the potency of cisplatin in ovarian cancer cell lines (A2780, CaOV3, OVCAR3 and cisplatin-resistant sub-clones). Preincubation with HDACi increased the cytotoxic potency of HSP90i, whereas preincubation with HSP90i had no effect. Preincubation with HSP90i or HDACi 48h prior to cisplatin enhanced the cisplatin potency significantly in all cell lines via apoptosis induction and affected the expression of apoptosis-relevant genes and proteins. For CaOV3CisR and A2780CisR, a preincubation with HDACi for 48–72 h led to complete reversal of cisplatin resistance. Furthermore, permanent presence of HDACi in sub-cytotoxic concentrations prevented the development of cisplatin resistance in A2780. However, triple combinations of HDACi, HSP90i and cisplatin were not superior to dual combinations. Overall, priming with HDACi sensitizes ovarian cancer cells to treatment with HSP90i or cisplatin and has an influence on the development of cisplatin resistance, both of which may contribute to an improved ovarian cancer treatment. Full article

(This article belongs to the Special Issue Survival Pathways Involved in Resistance to Apoptosis in Cancer)

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Review

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15 pages, 258 KiB

Open AccessReview

MicroRNAs and Apoptosis in Colorectal Cancer

by Hsiuying Wang

Int. J. Mol. Sci. 2020, 21(15), 5353; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21155353 - 28 Jul 2020

Cited by 67 | Viewed by 6215

Abstract

Colorectal cancer (CRC) is the third leading cause of cancer death in the world, and its incidence is rising in developing countries. Treatment with 5-Fluorouracil (5-FU) is known to improve survival in CRC patients. Most anti-cancer therapies trigger apoptosis induction to eliminate malignant cells. However, de-regulated apoptotic signaling allows cancer cells to escape this signaling, leading to therapeutic resistance. Treatment resistance is a major challenge in the development of effective therapies. The microRNAs (miRNAs) play important roles in CRC treatment resistance and CRC progression and apoptosis. This review discusses the role of miRNAs in contributing to the promotion or inhibition of apoptosis in CRC and the role of miRNAs in modulating treatment resistance in CRC cells. Full article

(This article belongs to the Special Issue Survival Pathways Involved in Resistance to Apoptosis in Cancer)

19 pages, 282 KiB

Open AccessReview

Cellular Mechanisms of Circulating Tumor Cells During Breast Cancer Metastasis

by Han-A Park, Spenser R. Brown and Yonghyun Kim

Int. J. Mol. Sci. 2020, 21(14), 5040; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21145040 - 17 Jul 2020

Cited by 29 | Viewed by 4084

Abstract

Circulating tumor cells (CTCs) are cancer cells that detach from the primary site and travel in the blood stream. A higher number of CTCs increases the risk of breast cancer metastasis, and it is inversely associated with the survival rates of patients with breast cancer. Although the numbers of CTCs are generally low and the majority of CTCs die in circulation, the survival of a few CTCs can seed the development of a tumor at a secondary location. An increasing number of studies demonstrate that CTCs undergo modification in response to the dynamic biophysical environment in the blood due in part to fluid shear stress. Fluid shear stress generates reactive oxygen species (ROS), triggers redox-sensitive cell signaling, and alters the function of intracellular organelles. In particular, the mitochondrion is an important target organelle in determining the metastatic phenotype of CTCs. In healthy cells, mitochondria produce adenosine triphosphate (ATP) via oxidative phosphorylation in the electron transport chain, and during oxidative phosphorylation, they produce physiological levels of ROS. Mitochondria also govern death mechanisms such as apoptosis and mitochondrial permeability transition pore opening to, in order eliminate unwanted or damaged cells. However, in cancer cells, mitochondria are dysregulated, causing aberrant energy metabolism, redox homeostasis, and cell death pathways that may favor cancer invasiveness. In this review, we discuss the influence of fluid shear stress on CTCs with an emphasis on breast cancer pathology, then discuss alterations of cellular mechanisms that may increase the metastatic potentials of CTCs. Full article

(This article belongs to the Special Issue Survival Pathways Involved in Resistance to Apoptosis in Cancer)

27 pages, 1301 KiB

Open AccessReview

Mechanisms of Apoptosis Resistance to NK Cell-Mediated Cytotoxicity in Cancer

by Christian Sordo-Bahamonde, Seila Lorenzo-Herrero, Ángel R. Payer, Segundo Gonzalez and Alejandro López-Soto

Int. J. Mol. Sci. 2020, 21(10), 3726; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21103726 - 25 May 2020

Cited by 56 | Viewed by 9230

Abstract

Natural killer (NK) cells are major contributors to immunosurveillance and control of tumor development by inducing apoptosis of malignant cells. Among the main mechanisms involved in NK cell-mediated cytotoxicity, the death receptor pathway and the release of granules containing perforin/granzymes stand out due to their efficacy in eliminating tumor cells. However, accumulated evidence suggest a profound immune suppression in the context of tumor progression affecting effector cells, such as NK cells, leading to decreased cytotoxicity. This diminished capability, together with the development of resistance to apoptosis by cancer cells, favor the loss of immunogenicity and promote immunosuppression, thus partially inducing NK cell-mediated killing resistance. Altered expression patterns of pro- and anti-apoptotic proteins along with genetic background comprise the main mechanisms of resistance to NK cell-related apoptosis. Herein, we summarize the main effector cytotoxic mechanisms against tumor cells, as well as the major resistance strategies acquired by tumor cells that hamper the extrinsic and intrinsic apoptotic pathways related to NK cell-mediated killing. Full article

(This article belongs to the Special Issue Survival Pathways Involved in Resistance to Apoptosis in Cancer)

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17 pages, 1108 KiB

Open AccessReview

Colorectal Cancer Invasion and Atrophy of the Enteric Nervous System: Potential Feedback and Impact on Cancer Progression

by Janusz Godlewski and Zbigniew Kmiec

Int. J. Mol. Sci. 2020, 21(9), 3391; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21093391 - 11 May 2020

Cited by 21 | Viewed by 4454

Abstract

Colorectal cancer (CRC) invasion within the large intestine wall results in the replacement of normal tissue architecture by tumour mass. Cancer cells digest the extracellular matrix (ECM) by the release of proteolytic enzymes. The disintegration of matrix ground substance activates several deposited growth factors which stimulate cell proliferation. Stromal (mainly fibroblasts), immune and cancer cells dominate in this area and become involved in a network of multimodal interactions which significantly induce proliferation of colon cancer cells, inhibit their apoptosis and promote their spreading within the local tumour microenvironment. Cancer invasion destroys nerve fibres and neurons of the local enteric nervous system (ENS) and induces subsequent atrophy of the submucosal and myenteric plexuses in areas adjacent to the cancer boundary. Interestingly, the reduction of plexuses’ size is accompanied by the increased number of galanin-immunoreactive neurons and increased galanin content in parts of the colon located close to the tumour. Galanin, a neuroprotective peptide, may inhibit the extrinsic pathway of apoptosis and in this way promote cancer cell survival. The possible role of acetylcholine and some ENS neuropeptides was also discussed. Invasion of cancer cells spreads along nerve fibres with the involvement of locally-released neutrophins which promote, via their specific receptors, cancer cell proliferation and pro-survival signalling pathways. Thus, during CRC development cancer cells and neurons of the ENS release many neurotransmitters/neuropeptides which affect key cellular signalling pathways promoting cancer cell proliferation and pro-survival phenotype. The multiple interactions between ENS neurons, cancer cells and other cell types present in the colon wall increase cancer cell invasiveness and have a negative impact on the course of CRC. Full article

(This article belongs to the Special Issue Survival Pathways Involved in Resistance to Apoptosis in Cancer)

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