scholarly journals ARID1A serves as a receivable biomarker for the resistance to EGFR-TKIs in non-small cell lung cancer

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Dantong Sun ◽  
Fei Teng ◽  
Puyuan Xing ◽  
Junling Li
Keyword(s):  
Epithelial To Mesenchymal Transition ◽  
Checkpoint Inhibitors ◽  
Mesenchymal Transition ◽  
Angiogenic Therapy ◽  
Chromatin Remodeling Complexes ◽  
Nsclc Patients ◽  
Small Molecular Inhibitors ◽  
Egfr Tkis ◽  
Expression Loss

AbstractARID1A is a key component of the SWI/SNF chromatin remodeling complexes which is important for the maintaining of biological processes of cells. Recent studies had uncovered the potential role of ARID1A alterations or expression loss in the therapeutic sensitivity of cancers, but the studies in this field requires to be further summarized and discussed. Therefore, we proposed a series of mechanisms related to the resistance to EGFR-TKIs induced by ARID1A alterations or expression loss and the potential therapeutic strategies to overcome the resistance based on published studies. It suggested that ARID1A alterations or expression loss might be the regulators in PI3K/Akt, JAK/STAT and NF-κB signaling pathways which are strongly associated with the resistance to EGFR-TKIs in NSCLC patients harboring sensitive EGFR mutations. Besides, ARID1A alterations or expression loss could lead to the resistance to EGFR-TKIs via a variety of processes during the tumorigenesis and development of cancers, including epithelial to mesenchymal transition, angiogenesis and the inhibition of apoptosis. Based on the potential mechanisms related to ARID1A, we summarized that the small molecular inhibitors targeting ARID1A or PI3K/Akt pathway, the anti-angiogenic therapy and immune checkpoint inhibitors could be used for the supplementary treatment for EGFR-TKIs among NSCLC patients harboring the concomitant alterations of sensitive EGFR mutations and ARID1A.

scholarly journals Integrin-Mediated TGFβ Activation Modulates the Tumour Microenvironment

Cancers ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1221 ◽  
Author(s):  
Brown ◽  
Marshall
Keyword(s):  
Transforming Growth Factor Beta ◽  
Epithelial To Mesenchymal Transition ◽  
Transforming Growth Factor ◽  
Checkpoint Inhibitors ◽  
Clinical Success ◽  
Immune Surveillance ◽  
Tumour Microenvironment ◽  
Mesenchymal Transition ◽  
Potential Benefits

TGFβ (transforming growth factor-beta) is a pleotropic cytokine with contrasting effects in cancer. In normal tissue and early tumours, TGFβ acts as a tumour suppressor, limiting proliferation and inducing apoptosis. However, these effects are eventually abrogated by the loss or inactivation of downstream signalling within the TGFβ pathway, and in established tumours, TGFβ then acts as a tumour promotor through multiple mechanisms including inducing epithelial-to-mesenchymal transition (EMT), promoting formation of cancer-associated fibroblasts (CAFs) and increasing angiogenesis. TGFβ is secrereted as a large latent complex and is embedded in the extracellular matrix or held on the surface of cells and must be activated before mediating its multiple functions. Thus, whilst TGFβ is abundant in the tumour microenvironment (TME), its functionality is regulated by local activation. The αv-integrins are major activators of latent-TGFβ. The potential benefits of manipulating the immune TME have been highlighted by the clinical success of immune-checkpoint inhibitors in a number of solid tumour types. TGFβ is a potent suppressor of T-cell-mediated immune surveillance and a key cause of resistance to checkpoint inhibitors. Therefore, as certain integrins locally activate TGFβ, they are likely to have a role in the immunosuppressive TME, although this remains to be confirmed. In this review, we discussed the role of TGFβ in cancer, the role of integrins in activating TGFβ in the TME, and the potential benefits of targeting integrins to augment immunotherapies.

Association of epithelial to mesenchymal transition with efficacy of EGFR-TKIs in non-small cell lung cancer patients with EGFR wild type.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7535-7535
Author(s):  
Shengxiang Ren ◽  
ChunXia Su ◽  
Xiaoxia Chen ◽  
Jiayu Li ◽  
Bing Li ◽  
...  
Keyword(s):  
Epithelial To Mesenchymal Transition ◽  
Egfr Mutation ◽  
Response Rate ◽  
Wild Type ◽  
Small Cell Lung ◽  
Mesenchymal Phenotype ◽  
Mesenchymal Transition ◽  
Epithelial Phenotype ◽  
Nsclc Patients ◽  
Egfr Tkis

7535 Background: The epithelial to mesenchymal transition (EMT) is a fundamental biological process during which epithelial cells change to a mesenchymal phenotype, it has a profound impact on cancer progression and treatment. The purpose of this study was to investigate the role of EMT to predict the efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in advanced non-small cell lung cancer (NSCLC) patients. Methods: We evaluated the correlation between EMT and sensitivity to EGFR-TKIs in advanced NSCLC patients. Immunohistochemistry was used to examine the expression of EMT markers, E-cadherin, fibronectin, N-cadherin and vimentin and ARMs was used to detect the EGFR mutation in tumor specimens obtained before the treatment. The EMT phenotype status was determined according to the expression of E-cadherin, fibronectin, N-cadherin and vimentin. Results: 101 patients enrolled into this study and 97 had enough tissue to perform the EMT examination. The median age was 59 years old, male/female:56/45, never smoker/smoker: 71/30, adenocarcinoma/non-adeno: 73/28, PS 0-1/2-3: 83/18, Stage IIIB/IV: 2/99, 1st /2nd-4th line: 13/88. The response rate and progression free survival(PFS) in the whole population were 45.5% and 7.6 months respectively. EMT test revealed that 46(47.4%) samples were epithelial phenotype, while 51(52.6%) were mesenchymal phenotype. 38 of 79 patients harbour activating EGFR mutation. Among the patients with EGFR wild type or unknown status, patients with an epithelial phenotype had a higher response rate(40% Vs 17.6%, P=0.056) and significantly longer PFS(7.6 m Vs 3.8 m, P=0.045) than these with a mesenchymal phenotype. However, the response rate(85.7% Vs 64.7%, P=0.249) and PFS(15.2 m Vs 12.2 m, P=0.420) were similar in the patients with activated EGFR mutation. Conclusions: Patients with an epithelial phenotype got more benefit from the treatment of EGFR-TKIs in the advanced EGFR wild type NSCLC patients, which indicated that the EMT might be a potential marker to guide the individual therapy of EGFR-TKIs in this subpopulation.

The role of DUBs in the post-translational control of cell migration

2019 ◽  
Vol 63 (5) ◽  
pp. 579-594 ◽  
Author(s):  
Guillem Lambies ◽  
Antonio García de Herreros ◽  
Víctor M. Díaz
Keyword(s):  
Cell Migration ◽  
Translational Control ◽  
Epithelial To Mesenchymal Transition ◽  
Extracellular Matrix Remodeling ◽  
Matrix Remodeling ◽  
Mesenchymal Transition ◽  
Tgfβ Receptors ◽  
Fundamental Process ◽  
Multistep Process

Abstract Cell migration is a multifactorial/multistep process that requires the concerted action of growth and transcriptional factors, motor proteins, extracellular matrix remodeling and proteases. In this review, we focus on the role of transcription factors modulating Epithelial-to-Mesenchymal Transition (EMT-TFs), a fundamental process supporting both physiological and pathological cell migration. These EMT-TFs (Snail1/2, Twist1/2 and Zeb1/2) are labile proteins which should be stabilized to initiate EMT and provide full migratory and invasive properties. We present here a family of enzymes, the deubiquitinases (DUBs) which have a crucial role in counteracting polyubiquitination and proteasomal degradation of EMT-TFs after their induction by TGFβ, inflammatory cytokines and hypoxia. We also describe the DUBs promoting the stabilization of Smads, TGFβ receptors and other key proteins involved in transduction pathways controlling EMT.

scholarly journals The Role of Autophagy and lncRNAs in the Maintenance of Cancer Stem Cells

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1239
Author(s):  
Leila Jahangiri ◽  
Tala Ishola ◽  
Perla Pucci ◽  
Ricky M. Trigg ◽  
Joao Pereira ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Progression ◽  
Regulatory Networks ◽  
Epithelial To Mesenchymal Transition ◽  
Tumour Microenvironment ◽  
Repair Capacity ◽  
Mesenchymal Transition ◽  
Cellular Processes

Cancer stem cells (CSCs) possess properties such as self-renewal, resistance to apoptotic cues, quiescence, and DNA-damage repair capacity. Moreover, CSCs strongly influence the tumour microenvironment (TME) and may account for cancer progression, recurrence, and relapse. CSCs represent a distinct subpopulation in tumours and the detection, characterisation, and understanding of the regulatory landscape and cellular processes that govern their maintenance may pave the way to improving prognosis, selective targeted therapy, and therapy outcomes. In this review, we have discussed the characteristics of CSCs identified in various cancer types and the role of autophagy and long noncoding RNAs (lncRNAs) in maintaining the homeostasis of CSCs. Further, we have discussed methods to detect CSCs and strategies for treatment and relapse, taking into account the requirement to inhibit CSC growth and survival within the complex backdrop of cellular processes, microenvironmental interactions, and regulatory networks associated with cancer. Finally, we critique the computationally reinforced triangle of factors inclusive of CSC properties, the process of autophagy, and lncRNA and their associated networks with respect to hypoxia, epithelial-to-mesenchymal transition (EMT), and signalling pathways.

Dual role of Ovol2 on the germ cell lineage segregation during gastrulation in mouse embryogenesis

Development ◽  
2022 ◽  
Author(s):  
Yuki Naitou ◽  
Go Nagamatsu ◽  
Nobuhiko Hamazaki ◽  
Kenjiro Shirane ◽  
Masafumi Hayashi ◽  
...  
Keyword(s):  
Germ Cells ◽  
Splice Variant ◽  
Epithelial To Mesenchymal Transition ◽  
Functional Relationship ◽  
Germ Line ◽  
Primordial Germ Cells ◽  
Cell Lineage ◽  
Animal Kingdom ◽  
Mesenchymal Transition

In mammals, primordial germ cells (PGCs), the origin of the germ line, are specified from the epiblast at the posterior region where gastrulation simultaneously occurs, yet the functional relationship between PGC specification and gastrulation remains unclear. Here, we show that Ovol2, a transcription factor conserved across the animal kingdom, balances these major developmental processes by repressing the epithelial-to-mesenchymal transition (EMT) driving gastrulation and the upregulation of genes associated with PGC specification. Ovol2a, a splice variant encoding a repressor domain, directly regulates EMT-related genes and consequently induces re-acquisition of potential pluripotency during PGC specification, whereas Ovol2b, another splice variant missing the repressor domain, directly upregulates genes associated with PGC specification. Taken together, these results elucidate the molecular mechanism underlying allocation of the germ line among epiblast cells differentiating into somatic cells through gastrulation.

scholarly journals The Role of Circular RNAs in Keratinocyte Carcinomas

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 4240
Author(s):  
Thomas Meyer ◽  
Michael Sand ◽  
Lutz Schmitz ◽  
Eggert Stockfleth
Keyword(s):  
Epithelial To Mesenchymal Transition ◽  
Circular Rnas ◽  
Mesenchymal Transition ◽  
Rna Molecules ◽  
Factors Associated ◽  
New Therapeutic Approaches ◽  
Non Coding Rna ◽  
Micro Rnas ◽  
Pubmed Search

Keratinocyte carcinomas (KC) include basal cell carcinomas (BCC) and cutaneous squamous cell carcinomas (cSCC) and represents the most common cancer in Europe and North America. Both entities are characterized by a very high mutational burden, mainly UV signature mutations. Predominately mutated genes in BCC belong to the sonic hedgehog pathway, whereas, in cSCC, TP53, CDKN2A, NOTCH1/2 and others are most frequently mutated. In addition, the dysregulation of factors associated with epithelial to mesenchymal transition (EMT) was shown in invasive cSCC. The expression of factors associated with tumorigenesis can be controlled in several ways and include non-coding RNA molecules, such as micro RNAs (miRNA) long noncoding RNAs (lncRNA) and circular RNAs (circRNA). To update findings on circRNA in KC, we reviewed 13 papers published since 2016, identified in a PubMed search. In both BCC and cSCC, numerous circRNAs were identified that were differently expressed compared to healthy skin. Some of them were shown to target miRNAs that are also dysregulated in KC. Moreover, some studies confirmed the biological functions of individual circRNAs involved in cancer development. Thus, circRNAs may be used as biomarkers of disease and disease progression and represent potential targets of new therapeutic approaches for KC.

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