Selective Autophagy Regulates Cell Cycle in Cancer Therapy

Aberrant function of cell cycle regulators results in uncontrolled cell proliferation, making them attractive therapeutic targets in cancer treatment. Indeed, survival of many cancers exclusively relies on these proteins, and several specific inhibitors are in clinical use. Although the ubiquitin-proteasome system is responsible for the periodic quality control of cell cycle proteins during cell cycle progression, increasing evidence clearly demonstrates the intimate interaction between cell cycle regulation and selective autophagy, important homeostasis maintenance machinery. However, these studies have often led to divergent rather than unifying explanations due to complexity of the autophagy signaling network, the inconsistent functions between general autophagy and selective autophagy, and the different characteristics of autophagic substrates. In this review, we highlight current data illustrating the contradictory and important role of cell cycle proteins in regulating autophagy. We also focus on how selective autophagy acts as a central mechanism to maintain orderly DNA repair and genome integrity by degrading specific cell cycle proteins, regulating cell division, and promoting DNA damage repair. We further discuss the ways in which selective autophagy may impact the cell cycle regulators, since failure to appropriately remove these can interfere with cell death-related processes, including senescence and autophagy-related cell death. Imbalanced cell proliferation is ...
Source: Theranostics - Category: Molecular Biology Authors: Tags: Review Source Type: research

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In conclusion, our data show how oncogenic and tumor-suppressive drivers of cellular senescence act to regulate surveillance processes that can be circumvented to enable SnCs to elude immune recognition but can be reversed by cell surface-targeted interventions to purge the SnCs that persist in vitro and in patients. Since eliminating SnCs can prevent tumor progression, delay the onset of degenerative diseases, and restore fitness; since NKG2D-Ls are not widely expressed in healthy human tissues and NKG2D-L shedding is an evasion mechanism also employed by tumor cells; and since increasing numbers of B cells express NKG2D ...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
This study not only provides a promising strategy for facile nanolization of functional food composites with hydrophobic defects but also sheds light on their cardiac protection and action mechanisms against IR‐induced disease.
Source: Small - Category: Nanotechnology Authors: Tags: Full Paper Source Type: research
In this study, we investigated the molecular mechanisms by which the human TNBC cell line MDA-MB-231, expressing PD-L1, responds to atezolizumab, using RNA-Seq. Transcriptome analysis revealed 388 upregulated and 362 downregulated genes in response to atezolizumab treatment. The expression of selected genes, from RNA-Seq data, was subsequently validated using RT-qPCR in the MDA-MB-231 and MDA-MB-468 TNBC cells following atezolizumab treatment. Bioinformatics analysis revealed that atezolizumab downregulates genes promoting cell migration/invasion and metastasis, epithelial-mesenchymal transition (EMT), cell growth/prolifer...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
This study elucidates the potential to use mitochondria from different donors (PAMM) to treat UVR stress and possibly other types of damage or metabolic malfunctions in cells, resulting in not only in-vitro but also ex-vivo applications. Gene Therapy in Mice Alters the Balance of Macrophage Phenotypes to Slow Atherosclerosis Progression Atherosclerosis causes a sizable fraction of all deaths in our species. It is the generation of fatty deposits in blood vessel...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
In this study, we show the ability of U94 to exert its anticancer activity on three different TNBC cell lines by inhibiting DNA damage repair genes, cell cycle and eventually leading to cell death following activation of the intrinsic apoptotic pathway. Interestingly, we found that U94 acted synergistically with DNA-damaging drugs. Overall, we provide evidence that U94 is able to combat tumor cells with different mechanisms, thus attesting for the great potential of this molecule as a multi-target drug in cancer therapy.
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
Abstract The Tousled-like kinases (TLKs) are an evolutionarily conserved family of serine-threonine kinases that have been implicated in DNA replication, DNA repair, transcription, chromatin structure, viral latency, cell cycle checkpoint control and chromosomal stability in various organisms. The functions of the TLKs appear to depend largely on their ability to regulate the H3/H4 histone chaperone ASF1, although numerous TLK substrates have been proposed. Over the last few years, a clearer picture of TLK function has emerged through the identification of new partners, the definition of specific roles in developm...
Source: Cellular and Molecular Life Sciences : CMLS - Category: Cytology Authors: Tags: Cell Mol Life Sci Source Type: research
In this study, we have reviewed the important roles of HATs in different human malignancies.
Source: Current Cancer Therapy Reviews - Category: Cancer & Oncology Source Type: research
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Source: DNA Repair - Category: Genetics & Stem Cells Authors: Tags: DNA Repair (Amst) Source Type: research
oszik J, Székvölgyi L Abstract Unravelling the origin of genetic alterations from point mutations to chromosomal rearrangements was greatly enhanced by the discovery of RNA-DNA hybrids (R-loops) that behave as hotspots of genomic instability in a variety of organisms. Current models suggest that uncontrolled R-loops are a hazard to genome integrity, therefore, identifying proteins that are involved in recognising and signalling R-loop structures are of key importance. Herein we analysed key RNA-DNA hybrid binding proteins in humans taking advantage of large-scale gene expression, survival rate, and dru...
Source: DNA Repair - Category: Genetics & Stem Cells Authors: Tags: DNA Repair (Amst) Source Type: research
CONCLUSION: With the development of promising therapies to boost the innate immune response, there is significant potential for the expansion of the role of immunotherapy as an adjuvant to surgical treatment in colorectal cancer. PMID: 31216061 [PubMed - as supplied by publisher]
Source: The British Journal of Surgery - Category: Surgery Authors: Tags: Br J Surg Source Type: research
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