scholarly journals Autophagy in Viral Development and Progression of Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Alejandra Suares ◽  
María Victoria Medina ◽  
Omar Coso
Keyword(s):  
Cell Fate ◽  
Cell Transformation ◽  
Tumor Development ◽  
Lysosomal Hydrolases ◽  
Subsequent Degradation ◽  
Cellular Context ◽  
Tumor Transformation ◽  
Proliferation And Metastasis ◽  
Viral Development ◽  
Catabolic Process

Autophagy is a complex degradative process by which eukaryotic cells capture cytoplasmic components for subsequent degradation through lysosomal hydrolases. Although this catabolic process can be triggered by a great variety of stimuli, action in cells varies according to cellular context. Autophagy has been previously linked to disease development modulation, including cancer. Autophagy helps suppress cancer cell advancement in tumor transformation early stages, while promoting proliferation and metastasis in advanced settings. Oncoviruses are a particular type of virus that directly contribute to cell transformation and tumor development. Extensive molecular studies have revealed complex ways in which autophagy can suppress or improve oncovirus fitness while still regulating viral replication and determining host cell fate. This review includes recent advances in autophagic cellular function and emphasizes its antagonistic role in cancer cells.

Linking Lipid Metabolism with Cell Transformation and Tumor Progression

2020 ◽  
Vol 5 (4) ◽  
pp. 153-161
Author(s):  
Meng Si Zuo ◽  
◽  
Jia Yu Yang ◽  
Pei Yun Wang ◽  
Hai Ou Yang ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Lipid Metabolism ◽  
Inflammatory Cell ◽  
Cell Transformation ◽  
Essential Fatty Acids ◽  
Tumor Development ◽  
The Body ◽  
Tumor Transformation ◽  
Major Nutrients ◽  
Abnormal Lipid Metabolism

Carbohydrates, lipids, and proteins are the three major nutrients required by the human body. The lipids, comprising triglycerides, phospholipids, and sterols, provide energy and essential fatty acids for the body, and are required for the growth and maintenance of human cells and tissues. A variety of lipid molecules and their intermediates are involved in cell signaling and inflammation, and have been reported to promote tumor transformation and progression. Fatty acid biosynthetic enzymes are also involved in the lipid metabolism of tumors. Dyslipidemia is closely related to many solid tumors, and may both play a role in both tumorigenesis and be a consequence of tumor development. Therefore, abnormal lipid metabolism is strongly associated with tumor transformation and progression. This review discusses the signaling pathways, related genes, enzymes, and inflammatory cell factors involved in tumor lipid metabolism, as well as the roles of dyslipidemia in tumor transformation and progression. We believe the information provided will serve as valuable reference highlighting molecules that can be targeted to improve the treatment of tumors.

scholarly journals MiR-7 in Cancer Development

Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 325
Author(s):  
Petra Korać ◽  
Mariastefania Antica ◽  
Maja Matulić
Keyword(s):  
Cell Fate ◽  
Dominant Role ◽  
Tumor Development ◽  
Mrna Translation ◽  
Cell Types ◽  
Fine Tuning ◽  
Non Coding Rna ◽  
Tumor Types ◽  
Different Cell Types ◽  
The Brain

MicroRNAs (miRNAs) are short non-coding RNA involved in the regulation of specific mRNA translation. They participate in cellular signaling circuits and can act as oncogenes in tumor development, so-called oncomirs, as well as tumor suppressors. miR-7 is an ancient miRNA involved in the fine-tuning of several signaling pathways, acting mainly as tumor suppressor. Through downregulation of PI3K and MAPK pathways, its dominant role is the suppression of proliferation and survival, stimulation of apoptosis and inhibition of migration. Besides these functions, it has numerous additional roles in the differentiation process of different cell types, protection from stress and chromatin remodulation. One of the most investigated tissues is the brain, where its downregulation is linked with glioblastoma cell proliferation. Its deregulation is found also in other tumor types, such as in liver, lung and pancreas. In some types of lung and oral carcinoma, it can act as oncomir. miR-7 roles in cell fate determination and maintenance of cell homeostasis are still to be discovered, as well as the possibilities of its use as a specific biotherapeutic.

The Drosophila orphan nuclear receptor seven-up requires the Ras pathway for its function in photoreceptor determination

Development ◽  
1995 ◽  
Vol 121 (1) ◽  
pp. 225-235 ◽  
Author(s):  
G. Begemann ◽  
A.M. Michon ◽  
L. vd Voorn ◽  
R. Wepf ◽  
M. Mlodzik
Keyword(s):  
Cell Fate ◽  
Nuclear Receptor ◽  
Egf Receptor ◽  
Cell Transformation ◽  
Orphan Nuclear Receptor ◽  
Loss Of Function ◽  
Cone Cell ◽  
Ras Pathway ◽  
Protein Levels ◽  
Cone Cells

The Drosophila seven-up (svp) gene specifies outer photoreceptor cell fate in eye development and encodes an orphan nuclear receptor with two isoforms. Transient expression under the sevenless enhancer of either svp isoform leads to a dosage-dependent transformation of cone cells into R7 photoreceptors, and at a lower frequency, R7 cells into outer photoreceptors. To investigate the cellular pathways involved, we have taken advantage of the dosage sensitivity and screened for genes that modify this svp-induced phenotype. We show that an active Ras pathway is essential for the function of both Svp isoforms. Loss-of-function mutations in components of the Ras signal transduction cascade act as dominant suppressors of the cone cell transformation, whilst loss-of-function mutations in negative regulators of Ras-activity act as dominant enhancers. Furthermore, Svp-mediated transformation of cone cells to outer photoreceptors, reminiscent of its wild-type function in specifying R3/4 and R1/6 identity, requires an activated Ras pathway in the same cells, or alternatively dramatic increase in ectopic Svp protein levels. Our results indicate that svp is only fully functional in conjunction with activated Ras. Since we find that mutations in the Egf-receptor are also among the strongest suppressors of svp-mediated cone cell transformation, we propose that the Ras activity in cone cells is due to low level Egfr signaling. Several models that could account for the observed svp regulation by the Ras pathway are discussed.

scholarly journals Non-cell-autonomous promotion of pluripotency induction mediated by YAP

2018 ◽  
Author(s):  
Amaleah Hartman ◽  
Xiao Hu ◽  
Xinyue Chen ◽  
Anna E. Eastman ◽  
Cindy Yang ◽  
...  
Keyword(s):  
Cell Fate ◽  
Pluripotent Stem Cells ◽  
Cell Types ◽  
Matricellular Proteins ◽  
Fate Control ◽  
Promotional Effect ◽  
Cellular Context ◽  
Opposing Effects ◽  
Cell Fate Control ◽  
Heterologous Cell

SUMMARYWhile Yes-associated protein (YAP) antagonizes pluripotency during early embryogenesis, it has also been shown to promote stemness of multiple stem cell types, including pluripotent stem cells. Whether cellular context underlies these distinct functions of YAP in pluripotency remains unclear. Here, we establish that depending on the specific cells in which it is expressed, YAP exhibits opposing effects on pluripotency induction from somatic cells. Specifically, YAP inhibits pluripotency induction cell-autonomously but promotes it non-cell-autonomously. For its non-cell-autonomous role, YAP alters the expression of many secreted and matricellular proteins including CYR61, which recapitulates the promotional effect when added as a recombinant protein. Thus, we define a unique YAP-driven non-cell-autonomous process that enhances pluripotency induction. Our work highlights the importance of considering the distinct contributions from heterologous cell types in deciphering the mechanism of cell fate control and calls for careful re-examination of the co-existing bystander cells in complex cultures or tissues.

scholarly journals Cellular context-dependent consequences of Apc mutations on gene regulation and cellular behavior

2017 ◽  
Vol 114 (4) ◽  
pp. 758-763 ◽  
Author(s):  
Kyoichi Hashimoto ◽  
Yosuke Yamada ◽  
Katsunori Semi ◽  
Masaki Yagi ◽  
Akito Tanaka ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Tumor Cells ◽  
Critical Role ◽  
Tumor Development ◽  
Cell Lineage ◽  
Genetic Rescue ◽  
Cellular Behavior ◽  
Cellular Context ◽  
Context Dependent

The spectrum of genetic mutations differs among cancers in different organs, implying a cellular context-dependent effect for genetic aberrations. However, the extent to which the cellular context affects the consequences of oncogenic mutations remains to be fully elucidated. We reprogrammed colon tumor cells in an ApcMin/+ (adenomatous polyposis coli) mouse model, in which the loss of the Apc gene plays a critical role in tumor development and subsequently, established reprogrammed tumor cells (RTCs) that exhibit pluripotent stem cell (PSC)-like signatures of gene expression. We show that the majority of the genes in RTCs that were affected by Apc mutations did not overlap with the genes affected in the intestine. RTCs lacked pluripotency but exhibited an increased expression of Cdx2 and a differentiation propensity that was biased toward the trophectoderm cell lineage. Genetic rescue of the mutated Apc allele conferred pluripotency on RTCs and enabled their differentiation into various cell types in vivo. The redisruption of Apc in RTC-derived differentiated cells resulted in neoplastic growth that was exclusive to the intestine, but the majority of the intestinal lesions remained as pretumoral microadenomas. These results highlight the significant influence of cellular context on gene regulation, cellular plasticity, and cellular behavior in response to the loss of the Apc function. Our results also imply that the transition from microadenomas to macroscopic tumors is reprogrammable, which underscores the importance of epigenetic regulation on tumor promotion.

scholarly journals E2A-PBX1 functions as a coactivator for RUNX1 in acute lymphoblastic leukemia

Blood ◽  
2020 ◽  
Vol 136 (1) ◽  
pp. 11-23 ◽  
Author(s):  
Wen-Chieh Pi ◽  
Jun Wang ◽  
Miho Shimada ◽  
Jia-Wei Lin ◽  
Huimin Geng ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Cell Fate ◽  
Cell Transformation ◽  
Lymphoblastic Leukemia ◽  
Gene Activation ◽  
Chromosomal Translocation ◽  
Direct Interaction ◽  
Binding Activity ◽  
Specific Cell ◽  
Dna Binding Activity

Abstract E2A, a basic helix-loop-helix transcription factor, plays a crucial role in determining tissue-specific cell fate, including differentiation of B-cell lineages. In 5% of childhood acute lymphoblastic leukemia (ALL), the t(1,19) chromosomal translocation specifically targets the E2A gene and produces an oncogenic E2A-PBX1 fusion protein. Although previous studies have shown the oncogenic functions of E2A-PBX1 in cell and animal models, the E2A-PBX1–enforced cistrome, the E2A-PBX1 interactome, and related mechanisms underlying leukemogenesis remain unclear. Here, by unbiased genomic profiling approaches, we identify the direct target sites of E2A-PBX1 in t(1,19)–positive pre-B ALL cells and show that, compared with normal E2A, E2A-PBX1 preferentially binds to a subset of gene loci cobound by RUNX1 and gene-activating machineries (p300, MED1, and H3K27 acetylation). Using biochemical analyses, we further document a direct interaction of E2A-PBX1, through a region spanning the PBX1 homeodomain, with RUNX1. Our results also show that E2A-PBX1 binding to gene enhancers is dependent on the RUNX1 interaction but not the DNA-binding activity harbored within the PBX1 homeodomain of E2A-PBX1. Transcriptome analyses and cell transformation assays further establish a significant RUNX1 requirement for E2A-PBX1–mediated target gene activation and leukemogenesis. Notably, the RUNX1 locus itself is also directly activated by E2A-PBX1, indicating a multilayered interplay between E2A-PBX1 and RUNX1. Collectively, our study provides the first unbiased profiling of the E2A-PBX1 cistrome in pre-B ALL cells and reveals a previously unappreciated pathway in which E2A-PBX1 acts in concert with RUNX1 to enforce transcriptome alterations for the development of pre-B ALL.

scholarly journals HIC1 and RassF1A Methylation Attenuates Tubulin Expression and Cell Stiffness in Cancer

2018 ◽  
Vol 19 (10) ◽  
pp. 2884 ◽  
Author(s):  
Chih-Cheng Chen ◽  
Bo-Ching He ◽  
Yao-Li Chen ◽  
Kuan-Der Lee ◽  
Chun-Hsin Tung ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Cultured Cells ◽  
Cell Transformation ◽  
Tumor Development ◽  
Cellular Transformation ◽  
Cell Stiffness ◽  
Physiological Status ◽  
Rassf1a Methylation ◽  
Potential Biomarker

Cell stiffness is a potential biomarker for monitoring cellular transformation, metastasis, and drug resistance development. Environmental factors relayed into the cell may result in formation of inheritable markers (e.g., DNA methylation), which provide selectable advantages (e.g., tumor development-favoring changes in cell stiffness). We previously demonstrated that targeted methylation of two tumor suppressor genes, hypermethylated in cancer 1 (HIC1) and Ras-association domain family member 1A (RassF1A), transformed mesenchymal stem cells (MSCs). Here, transformation-associated cytoskeleton and cell stiffness changes were evaluated. Atomic force microscopy (AFM) was used to detect cell stiffness, and immunostaining was used to measure cytoskeleton expression and distribution in cultured cells as well as in vivo. HIC1 and RassF1A methylation (me_HR)-transformed MSCs developed into tumors that clonally expanded in vivo. In me_HR-transformed MSCs, cell stiffness was lost, tubulin expression decreased, and F-actin was disorganized; DNA methylation inhibitor treatment suppressed their tumor progression, but did not fully restore their F-actin organization and stiffness. Thus, me_HR-induced cell transformation was accompanied by the loss of cellular stiffness, suggesting that somatic epigenetic changes provide inheritable selection markers during tumor propagation, but inhibition of oncogenic aberrant DNA methylation cannot restore cellular stiffness fully. Therefore, cell stiffness is a candidate biomarker for cells’ physiological status.

scholarly journals The Role of Ras-Associated Protein 1 (Rap1) in Cancer: Bad Actor or Good Player?

Biomedicines ◽  
2020 ◽  
Vol 8 (9) ◽  
pp. 334
Author(s):  
Chin-King Looi ◽  
Ling-Wei Hii ◽  
Siew Ching Ngai ◽  
Chee-Onn Leong ◽  
Chun-Wai Mai
Keyword(s):  
Cancer Progression ◽  
Tumor Development ◽  
Negative Regulator ◽  
T Cell Anergy ◽  
Promising Therapeutic Target ◽  
Life Threatening ◽  
Proliferation And Metastasis ◽  
Life Threatening Event ◽  
Tumor Proliferation And Metastasis

Metastasis is known as the most life-threatening event in cancer patients. In principle, the immune system can prevent tumor development. However, dysfunctional T cells may fail to eliminate the tumor cells effectively and provide additional survival advantages for tumor proliferation and metastasis. Constitutive activation of Ras-associated protein1 (Rap1) has not only led to T cell anergy, but also inhibited autophagy and supported cancer progression through various oncogenic events. Inhibition of Rap1 activity with its negative regulator, Rap1GAP, impairs tumor progression. However, active Rap1 reduces tumor invasion in some cancers, indicating that the pleiotropic effects of Rap1 signaling in cancers could be cancer-specific. All in all, targeting Rap1 signaling and its regulators could potentially control carcinogenesis, metastasis, chemoresistance and immune evasion. Rap1GAP could be a promising therapeutic target in combating cancer.

scholarly journals Identification of a new common provirus integration site in gross passage A murine leukemia virus-induced mouse thymoma DNA.

1987 ◽  
Vol 7 (1) ◽  
pp. 512-522 ◽  
Author(s):  
R Villemur ◽  
Y Monczak ◽  
E Rassart ◽  
C Kozak ◽  
P Jolicoeur
Keyword(s):  
T Cell ◽  
Murine Leukemia Virus ◽  
Cell Transformation ◽  
Integration Site ◽  
Leukemia Virus ◽  
Tumor Development ◽  
Mouse Strains ◽  
Mouse Tumor ◽  
Provirus Integration ◽  
Murine Leukemia

The Gross passage A murine leukemia virus (MuLV) induced T-cell leukemia of clonal (or oligoclonal) origin in inoculated mice. To study the role of the integrated proviruses in these tumor cells, we cloned several newly integrated proviruses (with their flanking cellular sequences) from a single tumor in procaryotic vectors. With each of the five clones obtained, a probe was prepared from the cellular sequences flanking the provirus. With one such probe (SS8), we screened several Gross passage A MuLV-induced SIM.S mouse tumor DNAs and found that, in 11 of 40 tumors, a provirus was integrated into a common region designated Gin-1. A 26-kilobase-pair sequence of Gin-1 was cloned from two lambda libraries, and a restriction map was derived. All proviruses were integrated as a cluster in the same orientation within a 5-kilobase-pair region of Gin-1, and most of them had a recombinant structure of the mink cell focus-forming virus type. The frequency of Gin-1 occupancy by provirus was much lower in thymoma induced by other strains of MuLV in other mouse strains. Using somatic-cell hybrid DNAs, we mapped Gin-1 on mouse chromosome 19. Gin-1 was not homologous to 16 known oncogenes and was distinct from the other common regions for provirus integration previously described. Therefore, Gin-1 appears to represent a new common provirus integration region. The integration of a provirus within Gin-1 might be an important event leading to T-cell transformation, and the Gin-1 region might harbor sequences which are involved in tumor development.

scholarly journals MicroRNAs in Cancer: Small Molecules With a Huge Impact

2009 ◽  
Vol 27 (34) ◽  
pp. 5848-5856 ◽  
Author(s):  
Marilena V. Iorio ◽  
Carlo M. Croce
Keyword(s):  
Small Molecules ◽  
Expression Profiling ◽  
Target Genes ◽  
Current Knowledge ◽  
Tumor Development ◽  
Microrna Expression ◽  
Cellular Context ◽  
Huge Impact ◽  
Therapeutic Tools ◽  
Oncosuppressor Genes

Every cellular process is likely to be regulated by microRNAs, and an aberrant microRNA expression signature is a hallmark of several diseases, including cancer. MicroRNA expression profiling has indeed provided evidence of the association of these tiny molecules with tumor development and progression. An increasing number of studies have then demonstrated that microRNAs can function as potential oncogenes or oncosuppressor genes, depending on the cellular context and on the target genes they regulate. Here we review our current knowledge about the involvement of microRNAs in cancer and their potential as diagnostic, prognostic, and therapeutic tools.

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