scholarly journals Hypoxia-Driven Effects in Cancer: Characterization, Mechanisms, and Therapeutic Implications

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 678
Author(s):  
Rachel Shi ◽  
Chengheng Liao ◽  
Qing Zhang
Keyword(s):  
Epithelial To Mesenchymal Transition ◽  
Mitochondrial Dynamics ◽  
Therapy Resistance ◽  
Cell Phenotype ◽  
Cancer Treatments ◽  
Transcriptional Responses ◽  
Mesenchymal Transition ◽  
Therapeutic Implications ◽  
Unfolded Protein ◽  
The Unfolded Protein Response

Hypoxia, a common feature of solid tumors, greatly hinders the efficacy of conventional cancer treatments such as chemo-, radio-, and immunotherapy. The depletion of oxygen in proliferating and advanced tumors causes an array of genetic, transcriptional, and metabolic adaptations that promote survival, metastasis, and a clinically malignant phenotype. At the nexus of these interconnected pathways are hypoxia-inducible factors (HIFs) which orchestrate transcriptional responses under hypoxia. The following review summarizes current literature regarding effects of hypoxia on DNA repair, metastasis, epithelial-to-mesenchymal transition, the cancer stem cell phenotype, and therapy resistance. We also discuss mechanisms and pathways, such as HIF signaling, mitochondrial dynamics, exosomes, and the unfolded protein response, that contribute to hypoxia-induced phenotypic changes. Finally, novel therapeutics that target the hypoxic tumor microenvironment or interfere with hypoxia-induced pathways are reviewed.

scholarly journals Control of Tumor Progression by Angiocrine Factors

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2610
Author(s):  
Elisenda Alsina-Sanchis ◽  
Ronja Mülfarth ◽  
Andreas Fischer
Keyword(s):  
Endothelial Cells ◽  
Tumor Progression ◽  
Cancer Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Therapy Resistance ◽  
Cell Phenotype ◽  
Long Distance ◽  
Mesenchymal Transition ◽  
Membrane Bound ◽  
Angiocrine Factors

Tumor progression, therapy resistance and metastasis are profoundly controlled by the tumor microenvironment. The contribution of endothelial cells to tumor progression was initially only attributed to the formation of new blood vessels (angiogenesis). Research in the last decade has revealed however that endothelial cells control their microenvironment through the expression of membrane-bound and secreted factors. Such angiocrine functions are frequently hijacked by cancer cells, which deregulate the signaling pathways controlling the expression of angiocrine factors. Here, we review the crosstalk between cancer cells and endothelial cells and how this contributes to the cancer stem cell phenotype, epithelial to mesenchymal transition, immunosuppression, remodeling of the extracellular matrix and intravasation of cancer cells into the bloodstream. We also address the long-distance crosstalk of a primary tumor with endothelial cells at the pre-metastatic niche and how this contributes to metastasis.

scholarly journals The E-Cadherin and N-Cadherin Switch in Epithelial-to-Mesenchymal Transition: Signaling, Therapeutic Implications, and Challenges

Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1118 ◽  
Author(s):  
Loh ◽  
Chai ◽  
Tang ◽  
Wong ◽  
Sethi ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Epithelial To Mesenchymal Transition ◽  
Human Cancer ◽  
Invasion And Metastasis ◽  
Cancer Treatments ◽  
Future Directions ◽  
Mesenchymal Transition ◽  
Therapeutic Implications ◽  
Cadherin Switch ◽  
E Cadherin

Epithelial-to-Mesenchymal Transition (EMT) has been shown to be crucial in tumorigenesis where the EMT program enhances metastasis, chemoresistance and tumor stemness. Due to its emerging role as a pivotal driver of tumorigenesis, targeting EMT is of great therapeutic interest in counteracting metastasis and chemoresistance in cancer patients. The hallmark of EMT is the upregulation of N-cadherin followed by the downregulation of E-cadherin, and this process is regulated by a complex network of signaling pathways and transcription factors. In this review, we summarized the recent understanding of the roles of E- and N-cadherins in cancer invasion and metastasis as well as the crosstalk with other signaling pathways involved in EMT. We also highlighted a few natural compounds with potential anti-EMT property and outlined the future directions in the development of novel intervention in human cancer treatments. We have reviewed 287 published papers related to this topic and identified some of the challenges faced in translating the discovery work from bench to bedside.

scholarly journals Endogenous Anti-Cancer Candidates in GPCR, ER Stress, and EMT

Biomedicines ◽  
2020 ◽  
Vol 8 (10) ◽  
pp. 402
Author(s):  
Rohit Gundamaraju ◽  
Wenying Lu ◽  
Iman Azimi ◽  
Rajaraman Eri ◽  
Sukhwinder Singh Sohal
Keyword(s):  
Er Stress ◽  
Cancer Progression ◽  
Epithelial To Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Unfolded Protein ◽  
Anti Cancer ◽  
Clinical Drugs ◽  
The Unfolded Protein Response ◽  
Protein Response ◽  
External Stimuli

The majority of cellular responses to external stimuli are mediated by receptors such as G protein-coupled receptors (GPCRs) and systems including endoplasmic reticulum stress (ER stress). Since GPCR signalling is pivotal in numerous malignancies, they are widely targeted by a number of clinical drugs. Cancer cells often negatively modulate GPCRs in order to survive, proliferate and to disseminate. Similarly, numerous branches of the unfolded protein response (UPR) act as pro-survival mediators and are involved in promoting cancer progression via mechanisms such as epithelial to mesenchymal transition (EMT). However, there are a few proteins among these groups which impede deleterious effects by orchestrating the pro-apoptotic phenomenon and paving a therapeutic pathway. The present review exposes and discusses such critical mechanisms and some of the key processes involved in carcinogenesis.

scholarly journals Modulation of Epithelial to Mesenchymal Transition Signaling Pathways by Olea Europaea and Its Active Compounds

2019 ◽  
Vol 20 (14) ◽  
pp. 3492 ◽  
Author(s):  
Rabiatul Adawiyah Razali ◽  
Yogeswaran Lokanathan ◽  
Muhammad Dain Yazid ◽  
Ayu Suraya Ansari ◽  
Aminuddin Bin Saim ◽  
...  
Keyword(s):  
Olea Europaea ◽  
Epithelial To Mesenchymal Transition ◽  
Epithelial Mesenchymal Transition ◽  
Healing Process ◽  
Mesenchymal Cell ◽  
Cell Phenotype ◽  
Wound Healing Process ◽  
Active Compounds ◽  
Mesenchymal Transition ◽  
Olea Europaéa

Epithelial-mesenchymal transition (EMT) is a significant dynamic process that causes changes in the phenotype of epithelial cells, changing them from their original phenotype to the mesenchymal cell phenotype. This event can be observed during wound healing process, fibrosis and cancer. EMT-related diseases are usually caused by inflammation that eventually leads to tissue remodeling in the damaged tissue. Prolonged inflammation causes long-term EMT activation that can lead to tissue fibrosis or cancer. Due to activation of EMT by its signaling pathway, therapeutic approaches that modulate that pathway should be explored. Olea europaea (OE) is well-known for its anti-inflammatory effects and abundant beneficial active compounds. These properties are presumed to modulate EMT events. This article reviews recent evidence of the effects of OE and its active compounds on EMT events and EMT-related diseases. Following evidence from the literature, it was shown that OE could modulate TGFβ/SMAD, AKT, ERK, and Wnt/β-catenin pathways in EMT due to a potent active compound that is present therein.

Deeper Insight in Metastatic Cancer progression;Epithelial-to-Mesenchymal Transition and Genomic Instability: implications on treatment resistance

2021 ◽  
Vol 21 ◽  
Author(s):  
Kenneth Omabe ◽  
Sandra Uduituma ◽  
David Igwe ◽  
Maxwell Omabe
Keyword(s):  
Dna Damage ◽  
Cancer Treatment ◽  
Epithelial To Mesenchymal Transition ◽  
Dna Damage Repair ◽  
Treatment Resistance ◽  
Therapy Resistance ◽  
Cellular Reprogramming ◽  
Repair System ◽  
Mesenchymal Transition ◽  
Damage Repair

: Therapy resistance remains the major obstacle to successful cancer treatment. Epithelial-to- mesenchymal transition [EMT], a cellular reprogramming process involved in embryogenesis and organ development and regulated by a number of transcriptional factors [EMT-TFs] such as ZEB1/2, is recognized for its role in tumor progression and metastasis. Recently, a growing body of evidence has implicated EMT in cancer therapy resistance but the actual mechanism that underlie this finding has remained elusive. For example, whether it is, the EMT states in itself or the EMT-TFs that modulates chemo or radio-resistance in cancer is still contentious. Here, we summarise the molecular mechanisms of EMT program and chemotherapeutic resistance in cancer with specific reference to DNA damage response [DDR]. We provide an insight into the molecular interplay that exist between EMT program and DNA repair machinery in cancer and how this interaction influences therapeutic response. We review conflicting studies linking EMT and drug resistance via the DNA damage repair axis. We draw scientific evidence demonstrating how several molecular signalling, including EMT-TFs work in operational harmony to induce EMT and confer stemness properties on the EMT-susceptible cells. We highlight the role of enhanced DNA damage repair system associated with EMT-derived stem cell-like states in promoting therapy resistance and suggest a multi-targeting modality in combating cancer treatment resistance.

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