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Cancers Jul 2021For over 20 years, it has been a dogma that once the integrity of mitochondria is disrupted and proapoptotic proteins that are normally located in the intermembrane... (Review)
Review
For over 20 years, it has been a dogma that once the integrity of mitochondria is disrupted and proapoptotic proteins that are normally located in the intermembrane space of mitochondria appeared in the cytoplasm, the process of cell death becomes inevitable. However, it has been recently shown that upon removal of the death signal, even at the stage of disturbance in the mitochondria, cells can recover and continue to grow. This phenomenon was named anastasis. Here, we will critically discuss the present knowledge concerning the mechanisms of cell death reversal, or development of anastasis, methods for its detection, and what role signaling from different intracellular compartments plays in anastasis stimulation.
PubMed: 34359573
DOI: 10.3390/cancers13153671 -
Cell Communication and Signaling : CCS Jun 2022Balanced cell death and survival are among the most important cell development and homeostasis pathways that can play a critical role in the onset or progress of... (Review)
Review
Balanced cell death and survival are among the most important cell development and homeostasis pathways that can play a critical role in the onset or progress of malignancy steps. Anastasis is a natural cell recovery pathway that rescues cells after removing the apoptosis-inducing agent or brink of death. The cells recuperate and recover to an active and stable state. So far, minimal knowledge is available about the molecular mechanisms of anastasis. Still, several involved pathways have been explained: recovery through mitochondrial outer membrane permeabilization, caspase cascade arrest, repairing DNA damage, apoptotic bodies formation, and phosphatidylserine. Anastasis can facilitate the survival of damaged or tumor cells, promote malignancy, and increase drug resistance and metastasis. Here, we noted recently known mechanisms of the anastasis process and underlying molecular mechanisms. Additionally, we summarize the consequences of anastatic mechanisms in the initiation and progress of malignancy, cancer cell metastasis, and drug resistance. Video Abstract.
Topics: Apoptosis; Cell Death; Cell Death Reversal; Cell Survival; DNA Damage; Humans; Neoplasms
PubMed: 35659306
DOI: 10.1186/s12964-022-00880-w -
Medicina 2020
Topics: Apoptosis; Cell Survival; HeLa Cells; Humans
PubMed: 32282324
DOI: No ID Found -
Royal Society Open Science Sep 2018Anastasis is a natural cell recovery phenomenon that rescues cells from the brink of death. Programmed cell death such as apoptosis has been traditionally assumed to be... (Review)
Review
Anastasis is a natural cell recovery phenomenon that rescues cells from the brink of death. Programmed cell death such as apoptosis has been traditionally assumed to be an intrinsically irreversible cascade that commits cells to a rapid and massive demolition. Interestingly, recent studies have demonstrated recovery of dying cells even at the late stages generally considered immutable. Here, we examine the evidence for anastasis in cultured cells and in animals, review findings illuminating the potential mechanisms of action, discuss the challenges of studying anastasis and explore new strategies to uncover the function and regulation of anastasis, the identification of which has wide-ranging physiological, pathological and therapeutic implications.
PubMed: 30839720
DOI: 10.1098/rsos.180442 -
Cell Death & Disease Jun 2023Chemotherapy is a common strategy to treat cancer. However, acquired resistance and metastasis are the major obstacles to successful treatment. Anastasis is a process by...
Chemotherapy is a common strategy to treat cancer. However, acquired resistance and metastasis are the major obstacles to successful treatment. Anastasis is a process by which cells survive executioner caspase activation when facing apoptotic stress. Here we demonstrate that colorectal cancer cells can undergo anastasis after transient exposure to chemotherapeutic drugs. Using a lineage tracing system to label and isolate cells that have experienced executioner caspase activation in response to drug treatment, we show that anastasis grants colorectal cancer cells enhanced migration, metastasis, and chemoresistance. Mechanistically, treatment with chemotherapeutic drugs induces upregulated expression of cIAP2 and activation of NFκB, which are required for cells to survive executioner caspase activation. The elevated cIAP2/NFκB signaling persists in anastatic cancer cells to promote migration and chemoresistance. Our study unveils that cIAP2/NFκB-dependent anastasis promotes acquired resistance and metastasis after chemotherapy.
Topics: Humans; Cell Death Reversal; Drug Resistance, Neoplasm; NF-kappa B; Colorectal Neoplasms; Caspases
PubMed: 37391410
DOI: 10.1038/s41419-023-05916-8 -
The Journal of Neuroscience : the... Mar 2022Anastasis is a recently described process in which cells recover after late-stage apoptosis activation. The functional consequences of anastasis for cells and tissues...
Anastasis is a recently described process in which cells recover after late-stage apoptosis activation. The functional consequences of anastasis for cells and tissues are not clearly understood. Using , rat and human cells and tissues, including analyses of both males and females, we present evidence that glia undergoing anastasis in the primary astrogliopathy Alexander disease subsequently express hallmarks of senescence. These senescent glia promote non-cell autonomous death of neurons by secreting interleukin family cytokines. Our findings demonstrate that anastasis can be dysfunctional in neurologic disease by inducing a toxic senescent population of astroglia. Under some conditions cells otherwise destined to die can be rescued just before death in a process called anastasis, or "rising from the dead." The fate and function of cells undergoing a near death experience is not well understood. Here, we find that in models and patient cells from Alexander disease, an important brain disorder in which glial cells promote neuronal dysfunction and death, anastasis of astrocytic glia leads to secretion of toxic signaling molecules and neurodegeneration. These studies demonstrate a previously unexpected deleterious consequence of rescuing cells on the brink of death and suggest therapeutic strategies for Alexander disease and related disorders of glia.
Topics: Alexander Disease; Animals; Apoptosis; Cell Death Reversal; Drosophila; Female; Humans; Male; Neuroglia; Neurons; Rats
PubMed: 35105675
DOI: 10.1523/JNEUROSCI.1659-21.2021 -
Chinese Journal of Cancer Jun 2017Multidrug resistance (MDR) occurs frequently after long-term chemotherapy, resulting in refractory cancer and tumor recurrence. Therefore, combatting MDR is an important... (Review)
Review
Multidrug resistance (MDR) occurs frequently after long-term chemotherapy, resulting in refractory cancer and tumor recurrence. Therefore, combatting MDR is an important issue. Autophagy, a self-degradative system, universally arises during the treatment of sensitive and MDR cancer. Autophagy can be a double-edged sword for MDR tumors: it participates in the development of MDR and protects cancer cells from chemotherapeutics but can also kill MDR cancer cells in which apoptosis pathways are inactive. Autophagy induced by anticancer drugs could also activate apoptosis signaling pathways in MDR cells, facilitating MDR reversal. Therefore, research on the regulation of autophagy to combat MDR is expanding and is becoming increasingly important. We summarize advanced studies of autophagy in MDR tumors, including the variable role of autophagy in MDR cancer cells.
Topics: Antineoplastic Agents; Apoptosis; Autophagy; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Humans; Neoplasms
PubMed: 28646911
DOI: 10.1186/s40880-017-0219-2 -
Cell Death and Differentiation Mar 2023Activation of executioner caspases was once considered as a point of no return in apoptosis. However, in recent years, accumulating evidence has demonstrated that cells...
Activation of executioner caspases was once considered as a point of no return in apoptosis. However, in recent years, accumulating evidence has demonstrated that cells can survive executioner caspase activation in response to apoptotic stimuli through a process called anastasis. In this study, we developed a reporter system, mCasExpress, to track mammalian cells that survive executioner caspase activation. We demonstrate that anastatic ovarian cancer cells acquire enhanced migration following their transient exposure to apoptotic stimulus TRAIL or Paclitaxel. Moreover, anastatic cancer cells secrete more pro-angiogenic factors that enable tumor angiogenesis, growth and metastasis. Mechanistically, we demonstrate that activation of p38 MAPK, which occurs in a caspase-dependent manner in response to apoptotic stress to promote anastasis, persists at a higher level in anastatic cancer cells even after removal of apoptotic stimuli. Importantly, p38 is essential for the elevated migratory and angiogenic capacity in the anastatic cells. Our work unveils anastasis as a potential driver of tumor angiogenesis and metastasis.
Topics: Animals; Humans; Female; p38 Mitogen-Activated Protein Kinases; Cell Death Reversal; Apoptosis; Caspases; Ovarian Neoplasms; Mammals
PubMed: 36447048
DOI: 10.1038/s41418-022-01081-1 -
Cancer Metastasis Reviews Jun 2020Apoptosis is a tightly controlled, coordinated cellular event responsible for inducing programmed cell death to rid the body of defective or unfit cells. Inhibition of... (Review)
Review
Apoptosis is a tightly controlled, coordinated cellular event responsible for inducing programmed cell death to rid the body of defective or unfit cells. Inhibition of apoptosis is, therefore, an essential process for cancer cells to harness. Genomic variants in apoptotic-controlling genes are highly prevalent in cancer and have been identified to induce pro-proliferation and pro-survival pathways, rendering cancer cells resistant to apoptosis. Traditional understanding of apoptosis defines it as an irreversible process; however, growing evidence suggests that apoptosis is a reversible process from which cells can escape, even after the activation of its most committed stages. The mechanism invoked to reverse apoptosis has been termed anastasis and poses challenges for the development and utilization of chemotherapeutic agents. Anastasis has also been identified as a mechanism by which cells can recover from apoptotic lesions and revert back to its previous functioning state. In this review, we intend to focus the attention of the reader on the comprehensive role of survival, metastasis, and epithelial mesenchymal transition (EMT), as well as DNA damage repair mechanisms in promoting anastasis. Additionally, we will emphasize the mechanistic consequences of anastasis on drug resistance and recent rational therapeutic approaches designed to combat this resistance.
Topics: Animals; Apoptosis; Cell Survival; DNA Damage; DNA Repair; Drug Resistance, Neoplasm; Epithelial-Mesenchymal Transition; Humans; Neoplasms
PubMed: 32020420
DOI: 10.1007/s10555-020-09866-x -
Current Opinion in Pediatrics Jun 2002Cerebral edema is the leading cause of death in children presenting in diabetic ketoacidosis and occurs in 0.2 to 1% of cases. The osmolar gradient caused by the high... (Review)
Review
Cerebral edema is the leading cause of death in children presenting in diabetic ketoacidosis and occurs in 0.2 to 1% of cases. The osmolar gradient caused by the high blood glucose results in water shift from the intracelluar fluid (ICF) to the extracellular fluid (ECF) space and contraction of cell volume. Correction with insulin and intravenous fluids can result in a rapid reduction in effective osmolarity, reversal of the fluid shift and the development of cerebral edema. The goals for treatment should be a combination of intravenous fluid and insulin that results in a gradual reduction of the effective osmolarity over a 36- to 48-hour period, thereby avoiding rapid expansion of the ICF compartment and brain swelling.
Topics: Animals; Brain Edema; Child; Diabetic Ketoacidosis; Fluid Therapy; Humans; Models, Animal
PubMed: 12011666
DOI: 10.1097/00008480-200206000-00001