The central role of mitochondria in the relationship between dietary lipids and cancer progression

Author(s):  
Alfonso Varela-López ◽  
Laura Vera-Ramírez ◽  
Francesca Giampieri ◽  
María D. Navarro-Hortal ◽  
Tamara Y. Forbes-Hernández ◽  
...  
Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 3061
Author(s):  
Francesca Aprile ◽  
Giovanni Bruno ◽  
Rossella Palma ◽  
Maria Teresa Mascellino ◽  
Cristina Panetta ◽  
...  

Gut microbiota plays an important role in human health. It may promote carcinogenesis and is related to several diseases of the gastrointestinal tract. This study of microbial dysbiosis in the etiology of colorectal adenoma aimed to investigate the possible causative role of microbiota in the adenoma–carcinoma sequence and its possible preventive role. A systematic, PRISMA-guided review was performed. The PubMed database was searched using “adenoma microbiota” and selecting original articles between January 2010 and May 2020 independently screened. A higher prevalence of Proteobacteria, Fusobacteria, and Bacteroidetes phyla was observed in the fecal luminal and mucosa-associated microbiota of patients with adenoma. However, other studies provided evidence of depletion of Clostridium, Faecalibacterium, Bacteroides and Romboutsia. Results on the relationship between adenoma endoscopic resection and microbiota were inconsistent. In conclusion, none of the analyzed studies developed a predictive model that could differentiate adenoma from non-adenoma patients, and therefore, to prevent cancer progression. The impact of adenoma’s endoscopic resection on microbiota was investigated, but the results were inconclusive. Further research in the field is required.


Author(s):  
Ismail Al-Janabi

Autophagy is a conserved homeostatic mechanism enabling cells to cope with various stresses. The pathways leading up to the activation of autophagy are interconnected with those of tumorigenesis. However, the relationship between the two events is not a straightforward one and very often context-dependent. Generally, autophagy appears to act against the tumor during the initiation stage and most often drives cancer progression subsequently. Published clinical trials for the treatment of various tumors, where autophagy was pharmacologically inhibited, were obtained and tabulated. Targeting autophagy for the treatment of tumors can be rewarding in the appropriate context, such as cancer type, grade, and microenvironment.


2020 ◽  
Vol 35 (1_suppl) ◽  
pp. 8-11 ◽  
Author(s):  
Paola Nisticò ◽  
Gennaro Ciliberto

Our view of cancer biology radically shifted from a “cancer-cell-centric” vision to a view of cancer as an organ disease. The concept that genetic and/or epigenetic alterations, at the basis of cancerogenesis, are the main if not the exclusive drivers of cancer development and the principal targets of therapy, has now evolved to include the tumor microenvironment in which tumor cells can grow, proliferate, survive, and metastasize only within a favorable environment. The interplay between cancer cells and the non-cellular and cellular components of the tumor microenvironment plays a fundamental role in tumor development and evolution both at the primary site and at the level of metastasis. The shape of the tumor cells and tumor mass is the resultant of several contrasting forces either pro-tumoral or anti-tumoral which have at the level of the tumor microenvironment their battle field. This crucial role of tumor microenvironment composition in cancer progression also dictates whether immunotherapy with immune checkpoint inhibitor antibodies is going to be efficacious. Hence, tumor microenvironment deconvolution has become of great relevance in order to identify biomarkers predictive of efficacy of immunotherapy. In this short paper we will briefly review the relationship between inflammation and cancer, and will summarize in 10 short points the key concepts learned so far and the open challenges to be solved.


2019 ◽  
Author(s):  
Roshina Thapa ◽  
Swetha Vasudevan ◽  
Mimi Abo-Ayoub Ashqar ◽  
Eli Reich ◽  
Nataly Kravchenko-Balasha ◽  
...  

AbstractCancer cells have an altered transcriptome which contributes to their altered behaviors compared to normal cells. Indeed, many tumors express high levels of genes participating in meiosis or kinetochore biology, but the role of this high expression has not been fully elucidated. In this study we explore the relationship between this overexpression and genome instability and transformation capabilities of cancer cells. For this, we obtained expression data from 5 different cancer types which were analyzed using computational information-theoretic analysis. We were able to show that highly expressed meiotic/kinetochore genes were enriched in the altered gene expression subnetworks characterizing unstable cancer types with high chromosome instability (CIN). However, altered subnetworks found in the cancers with low CIN did not include meiotic and kinetochore genes. Representative gene candidates, found by the analysis to be correlated with a CIN phenotype, were further explored by transfecting genomically-stable (HCT116) and unstable (MCF7) cancer cell lines with vectors overexpressing those genes. This overexpression resulted in an increase in the numbers of abnormal cell divisions and defective spindle formations and in increased transformation properties in stable cancer HCT116 cells. Interestingly, the same properties were less affected by the overexpressed genes in the unstable MCF7 cancer cells. Our results indicate that overexpression of both meiosis and kinetochore genes is capable of driving genomic instability and cancer progression.


Author(s):  
Fengying Gong ◽  
Yuchao Yang ◽  
Liangtao Wen ◽  
Congrong Wang ◽  
Jingjun Li ◽  
...  

Cells and tissues in the human body are subjected to mechanical forces of varying degrees, such as tension or pressure. During tumorigenesis, physical factors, especially mechanical factors, are involved in tumor development. As lung tissue is influenced by movements associated with breathing, it is constantly subjected to cyclical stretching and retraction; therefore, lung cancer cells and lung cancer-associated fibroblasts (CAFs) are constantly exposed to mechanical load. Thus, to better explore the mechanisms involved in lung cancer progression, it is necessary to consider factors involved in cell mechanics, which may provide a more comprehensive analysis of tumorigenesis. The purpose of this review is: 1) to provide an overview of the anatomy and tissue characteristics of the lung and the presence of mechanical stimulation; 2) to summarize the role of mechanical stretching in the progression of lung cancer; and 3) to describe the relationship between mechanical stretching and the lung cancer microenvironment, especially CAFs.


2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Anbang Wang ◽  
Aimin Jiang ◽  
Xinxin Gan ◽  
Zheng Wang ◽  
Jinming Huang ◽  
...  

Long noncoding RNAs play an essential role in bladder cancer progression. The role of long noncoding RNA EGFR-AS1 in bladder cancer needs further study. We used clinical specimens to analyze the relationship between EGFR-AS1 and bladder cancer patients’ characteristics. The functional experiments and mechanism studies were performed using qRT-PCR, transwell assay, survival analysis, and correlation analysis. We found that high expression of EGFR-AS1 was nearly related to aggressive bladder cancer and indicated poor prognosis for patients. The functional experiments in vivo and in vitro suggested that EGFR-AS1 promoted the proliferation and invasion of bladder cancer cells. Mechanically, EGFR-AS1 promoted the expression of EGFR by inhibiting the degradation of EGFR mRNA, thereby promoting the metastasis of bladder cancer. In addition, EGFR-AS1/EGFR may be involved in the immune-related pathways of bladder cancer. These studies indicate that the EGFR-AS1/EGFR pathway may be a potential diagnostic marker and therapeutic target for bladder cancer.


2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Jie Mei ◽  
Tiejun Wang ◽  
Shaojie Zhao ◽  
Yan Zhang

Osthole (OST) is a plant-derived compound that can inhibit the proliferation of tumor cells and has a tumor-suppressive effect in multiple types of cancers. However, the mechanisms of OST-mediated breast cancer (BrCa) inhibition were still largely unknown. In this study, we made full use of the GSE85871 dataset to identify potential targets of OST in BrCa via multiple bioinformatics analysis. Next, a series of in vitro experiments were conducted to check the role of GNG7 in BrCa and the relationship between OST and GNG7. Through a series of bioinformatics analyses, GNG7 was identified as a potential target of OST, which could be significant upregulated by OST exposure in BrCa cells. Besides, GNG7 was lowly expressed in BrCa tissues compared with normal breast tissues, and BrCa patients with low GNG7 expression had shorter overall survival (OS) and relapse-free survival (RFS) compared with those with high GNG7 expression. Moreover, GNG7 silencing significantly enhanced cell proliferation and inhibited apoptosis, and exogenous overexpression of GNG7 showed reverse effects on BrCa cells. Last but not least, GNG7 inhibition could notably rescue OST-mediated cytotoxic effects. In summary, we identified GNG7 as a novel target for OST in BrCa and a potential tumor suppressor. Thus, OST could be therapeutically beneficial for BrCa through a GNG7-dependent mechanism.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS9099-TPS9099
Author(s):  
Crispin T. Hiley ◽  
Tanya Ahmad ◽  
Mariam Jamal-Hanjani ◽  
Christopher Abbosh ◽  
Yenting Ngai ◽  
...  

TPS9099 Background: The importance of intratumour heterogeneity (ITH) is increasingly recognised as a driver of cancer progression and survival outcome. However understanding how tumour clonal heterogeneity impacts upon therapeutic outcome is still an area of unmet clinical and scientific need. The TRACERx trial (NCT01888601), a prospective study of patients with radically resected primary non-small cell lung cancer (NSCLC), aims to define the evolutionary trajectories of lung cancer in both space and time through genetic analysis of multi-region and longitudinal tumour sampling. DARWIN II is an investigator initiated study for patients who are enrolled within the TRACERx trial, or who have multi-region sequencing of their primary disease, but subsequently relapse with metastatic disease. This study will examine the role of intra-tumour heterogeneity and predicted neo-antigens on the anti-tumour activity of anti-PDL1 immunotherapy. Methods: This multicentre non-randomised phase II molecularly stratified umbrella study will examine how clonal dominance and ITH influence outcomes after treatment, offering a unique opportunity to decipher mechanisms of resistance to immunotherapy with anti-PDL1. These data will help improve future study design by developing greater understanding of patient selection for immunotherapies in patients with NSCLC. The relationship between ITH and cfDNA/CTCs will also be explored in DARWIN II. The study arms: Arm 1: Patients either -1) without an actionable mutation and PDL1 positive or 2) without an actionable mutation and PDL1 negative following first line cytotoxic chemotherapy - Atezolizumab. Arm 2: BRAFV600 - Vemurafenib. Arm 3: ALK/RET gene rearrangement - Alectinib. Arm 4: Her2 Amplification - Trastuzumab Emtansine. Primary Outcome Measures: Progression free survival (PFS), defined as the period between the date of registration to the date of subsequent progression or death will be assessed according to: Neo-antigen burden, mutational burden, ITH as assessed using an ITH ratio index and genomic instability as assessed using a weighted genome instability index (wGII). Trial Sponsor: University College London. Clinical trial information: NCT02314481.


2019 ◽  
Vol 11 (10) ◽  
pp. 920-929 ◽  
Author(s):  
Quan Yang ◽  
Jinyao Zhao ◽  
Wenjing Zhang ◽  
Dan Chen ◽  
Yang Wang

Abstract Alternative splicing is critical for human gene expression regulation, which plays a determined role in expanding the diversity of functional proteins. Importantly, alternative splicing is a hallmark of cancer and a potential target for cancer therapeutics. Based on the statistical data, breast cancer is one of the top leading causes of cancer-related deaths in women worldwide. Strikingly, alternative splicing is closely associated with breast cancer development. Here, we seek to provide a general review of the relationship between alternative splicing and breast cancer. We introduce the process of alternative splicing and its regulatory role in cancers. In addition, we highlight the functions of aberrant alternative splicing and mutations of splicing factors in breast cancer progression. Moreover, we discuss the role of alternative splicing in cancer drug resistance and the potential of being targets for cancer therapeutics.


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