scholarly journals Linking Cancer Stem Cell Plasticity to Therapeutic Resistance-Mechanism and Novel Therapeutic Strategies in Esophageal Cancer

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1481
Author(s):  
Chenghui Zhou ◽  
Ningbo Fan ◽  
Fanyu Liu ◽  
Nan Fang ◽  
Patrick S. Plum ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Resistance Mechanism ◽  
Therapy Resistance ◽  
Metabolic Reprogramming ◽  
Current Evidence ◽  
Mesenchymal Transition ◽  
Therapeutic Implications

Esophageal cancer (EC) is an aggressive form of cancer, including squamous cell carcinoma (ESCC) and adenocarcinoma (EAC) as two predominant histological subtypes. Accumulating evidence supports the existence of cancer stem cells (CSCs) able to initiate and maintain EAC or ESCC. In this review, we aim to collect the current evidence on CSCs in esophageal cancer, including the biomarkers/characterization strategies of CSCs, heterogeneity of CSCs, and the key signaling pathways (Wnt/β-catenin, Notch, Hedgehog, YAP, JAK/STAT3) in modulating CSCs during esophageal cancer progression. Exploring the molecular mechanisms of therapy resistance in EC highlights DNA damage response (DDR), metabolic reprogramming, epithelial mesenchymal transition (EMT), and the role of the crosstalk of CSCs and their niche in the tumor progression. According to these molecular findings, potential therapeutic implications of targeting esophageal CSCs may provide novel strategies for the clinical management of esophageal cancer.

Galectin-3: A factotum in carcinogenesis bestowing an archery for prevention

Tumor Biology ◽  
2021 ◽  
Vol 43 (1) ◽  
pp. 77-96
Author(s):  
T. Jeethy Ram ◽  
Asha Lekshmi ◽  
Thara Somanathan ◽  
K. Sujathan
Keyword(s):  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Therapy Resistance ◽  
Cellular Level ◽  
Clinical Samples ◽  
Innovative Strategy ◽  
Mesenchymal Transition ◽  
Galectin 3

Cancer metastasis and therapy resistance are the foremost hurdles in oncology at the moment. This review aims to pinpoint the functional aspects of a unique multifaceted glycosylated molecule in both intracellular and extracellular compartments of a cell namely galectin-3 along with its metastatic potential in different types of cancer. All materials reviewed here were collected through the search engines PubMed, Scopus, and Google scholar. Among the 15 galectins identified, the chimeric gal-3 plays an indispensable role in the differentiation, transformation, and multi-step process of tumor metastasis. It has been implicated in the molecular mechanisms that allow the cancer cells to survive in the intravascular milieu and promote tumor cell extravasation, ultimately leading to metastasis. Gal-3 has also been found to have a pivotal role in immune surveillance and pro-angiogenesis and several studies have pointed out the importance of gal-3 in establishing a resistant phenotype, particularly through the epithelial-mesenchymal transition process. Additionally, some recent findings suggest the use of gal-3 inhibitors in overcoming therapeutic resistance. All these reports suggest that the deregulation of these specific lectins at the cellular level could inhibit cancer progression and metastasis. A more systematic study of glycosylation in clinical samples along with the development of selective gal-3 antagonists inhibiting the activity of these molecules at the cellular level offers an innovative strategy for primary cancer prevention.

scholarly journals Exploring Hyperoxia Effects in Cancer—From Perioperative Clinical Data to Potential Molecular Mechanisms

Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1213
Author(s):  
Anca Irina Ristescu ◽  
Crina Elena Tiron ◽  
Adrian Tiron ◽  
Ioana Grigoras
Keyword(s):  
Cancer Patients ◽  
Cancer Progression ◽  
Cancer Biology ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Experimental Studies ◽  
Perioperative Period ◽  
Postoperative Recovery ◽  
Mesenchymal Transition ◽  
Oncological Treatment

Increased inspiratory oxygen concentration is constantly used during the perioperative period of cancer patients to prevent the potential development of hypoxemia and to provide an adequate oxygen transport to the organs, tissues and cells. Although the primary tumours are surgically removed, the effects of perioperative hyperoxia exposure on distal micro-metastases and on circulating cancer cells can potentially play a role in cancer progression or recurrence. In clinical trials, hyperoxia seems to increase the rate of postoperative complications and, by delaying postoperative recovery, it can alter the return to intended oncological treatment. The effects of supplemental oxygen on the long-term mortality of surgical cancer patients offer, at this point, conflicting results. In experimental studies, hyperoxia effects on cancer biology were explored following multiple pathways. In cancer cell cultures and animal models, hyperoxia increases the production of reactive oxygen species (ROS) and increases the oxidative stress. These can be followed by the induction of the expression of Brain-derived neurotrophic factor (BDNF) and other molecules involved in angiogenesis and by the promotion of various degrees of epithelial mesenchymal transition (EMT).

scholarly journals Role of Metabolic Reprogramming in Epithelial–Mesenchymal Transition (EMT)

2019 ◽  
Vol 20 (8) ◽  
pp. 2042 ◽  
Author(s):  
Hyunkoo Kang ◽  
Hyunwoo Kim ◽  
Sungmin Lee ◽  
HyeSook Youn ◽  
BuHyun Youn
Keyword(s):  
Tumor Progression ◽  
Tumor Cells ◽  
Molecular Mechanisms ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Metabolic Reprogramming ◽  
Metabolic Enzyme ◽  
Diverse Range ◽  
Mesenchymal Transition ◽  
Altered Glucose

Activation of epithelial–mesenchymal transition (EMT) is thought to be an essential step for cancer metastasis. Tumor cells undergo EMT in response to a diverse range of extra- and intracellular stimulants. Recently, it was reported that metabolic shifts control EMT progression and induce tumor aggressiveness. In this review, we summarize the involvement of altered glucose, lipid, and amino acid metabolic enzyme expression and the underlying molecular mechanisms in EMT induction in tumor cells. Moreover, we propose that metabolic regulation through gene-specific or pharmacological inhibition may suppress EMT and this treatment strategy may be applied to prevent tumor progression and improve anti-tumor therapeutic efficacy. This review presents evidence for the importance of metabolic changes in tumor progression and emphasizes the need for further studies to better understand tumor metabolism.

scholarly journals Epithelial–mesenchymal transition: role in cancer progression and the perspectives of antitumor treatment

Acta Naturae ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 4-23
Author(s):  
A. V. Gaponova ◽  
S. Rodin ◽  
A. A. Mazina ◽  
P. V. Volchkov
Keyword(s):  
Epithelial Cells ◽  
Tumor Progression ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Malignant Tumors ◽  
The Body ◽  
Epithelial Tissue ◽  
Mesenchymal Transition ◽  
Tumor Dissemination

About 90% of all malignant tumors are of epithelial nature. The epithelial tissue is characterized by a close interconnection between cells through cellcell interactions, as well as a tight connection with the basement membrane, which is responsible for cell polarity. These interactions strictly determine the location of epithelial cells within the body and are seemingly in conflict with the metastatic potential that many cancers possess (the main criteria for highly malignant tumors). Tumor dissemination into vital organs is one of the primary causes of death in patients with cancer. Tumor dissemination is based on the so-called epithelialmesenchymal transition (EMT), a process when epithelial cells are transformed into mesenchymal cells possessing high mobility and migration potential. More and more studies elucidating the role of the EMT in metastasis and other aspects of tumor progression are published each year, thus forming a promising field of cancer research. In this review, we examine the most recent data on the intracellular and extracellular molecular mechanisms that activate EMT and the role they play in various aspects of tumor progression, such as metastasis, apoptotic resistance, and immune evasion, aspects that have usually been attributed exclusively to cancer stem cells (CSCs). In conclusion, we provide a detailed review of the approved and promising drugs for cancer therapy that target the components of the EMT signaling pathways.

scholarly journals Cancer Chemoprevention: Current State of the Art

2014 ◽  
Vol 7 ◽  
pp. CGM.S11288 ◽  
Author(s):  
Kristin R. Landis-Piwowar ◽  
Neena R. Iyer
Keyword(s):  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Cancer Chemoprevention ◽  
Cancer Therapies ◽  
Metastatic Progression ◽  
Chemopreventive Agents ◽  
Mesenchymal Transition ◽  
Initiation Phase ◽  
Current State

The aim of cancer chemoprevention is disruption or delay of the molecular pathways that lead to carcinogenesis. Chemopreventive blocking and/or suppressing agents disrupt the molecular mechanisms that drive carcinogenesis such as DNA damage by reactive oxygen species, increased signal transduction to NF-κB, epigenomic deregulation, and the epithelial mesenchymal transition that leads to metastatic progression. Numerous dietary phytochemicals have been observed to inhibit the initiation phase of carcinogenesis, and therefore are useful in primary chemoprevention. Moreover, phytochemicals are capable of interfering with the molecular mechanisms of metastasis. Likewise, numerous synthetic compounds are relevant and clinically viable as chemopreventive agents during the fundamental stages of carcinogenesis. While molecularly targeted anti-cancer therapies are in constant stages of development, superior patient outcomes are observed if carcinogenic processes are prevented altogether. This article reviews the role of chemopreventive compounds in inhibition of cancer initiation and their ability to reduce cancer progression.

scholarly journals Dynamics of Phenotypic Heterogeneity Associated with EMT and Stemness during Cancer Progression

2019 ◽  
Vol 8 (10) ◽  
pp. 1542 ◽  
Author(s):  
Mohit Kumar Jolly ◽  
Toni Celià-Terrassa
Keyword(s):  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Relevant Literature ◽  
Phenotypic Heterogeneity ◽  
State Transitions ◽  
Strong Impact ◽  
Mesenchymal Transition ◽  
Cancer Aggressiveness

Genetic and phenotypic heterogeneity contribute to the generation of diverse tumor cell populations, thus enhancing cancer aggressiveness and therapy resistance. Compared to genetic heterogeneity, a consequence of mutational events, phenotypic heterogeneity arises from dynamic, reversible cell state transitions in response to varying intracellular/extracellular signals. Such phenotypic plasticity enables rapid adaptive responses to various stressful conditions and can have a strong impact on cancer progression. Herein, we have reviewed relevant literature on mechanisms associated with dynamic phenotypic changes and cellular plasticity, such as epithelial–mesenchymal transition (EMT) and cancer stemness, which have been reported to facilitate cancer metastasis. We also discuss how non-cell-autonomous mechanisms such as cell–cell communication can lead to an emergent population-level response in tumors. The molecular mechanisms underlying the complexity of tumor systems are crucial for comprehending cancer progression, and may provide new avenues for designing therapeutic strategies.

scholarly journals Metastatic suppression by DOC2B is mediated by inhibition of epithelial-mesenchymal transition and induction of senescence

2021 ◽  
Author(s):  
Samatha Bhat ◽  
Divya Adiga ◽  
Vaibhav Shukla ◽  
Kanive Parashiva Guruprasad ◽  
Shama Prasada Kabekkodu ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Tumor Growth ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Vesicle Trafficking ◽  
Critical Role ◽  
Anoikis Resistance ◽  
Mesenchymal Transition ◽  
Intracellular Vesicle

AbstractSenescence induction and epithelial-mesenchymal transition (EMT) events are the opposite sides of the spectrum of cancer phenotypes. The key molecules involved in these processes may get influenced or altered by genetic and epigenetic changes during tumor progression. Double C2-like domain beta (DOC2B), an intracellular vesicle trafficking protein of the double C2 protein family, plays a critical role in exocytosis, neurotransmitter release, and intracellular vesicle trafficking. DOC2B is repressed by DNA promoter hypermethylation and functions as a tumor growth regulator in cervical cancer. To date, the molecular mechanisms of DOC2B in cervical cancer progression and metastasis is elusive. Herein, the biological functions and molecular mechanisms regulated by DOC2B and its impact on senescence and EMT are described. DOC2B inhibition promotes proliferation, growth, and migration by relieving G0/G1-S arrest, actin remodeling, and anoikis resistance in Cal27 cells. It enhanced tumor growth and liver metastasis in nude mice with the concomitant increase in metastasis-associated CD55 and CD61 expression. Inhibition of EMT and promotion of senescence by DOC2B is a calcium-dependent process and accompanied by calcium-mediated interaction between DOC2B and CDH1. In addition, we have identified several EMT and senescence regulators as targets of DOC2B. We show that DOC2B may act as a metastatic suppressor by inhibiting EMT through induction of senescence via DOC2B-calcium-EMT-senescence axis. Graphical abstract

scholarly journals Therapy Resistance in Cancers: Phenotypic, Metabolic, Epigenetic and Tumour Microenvironmental Perspectives

2020 ◽  
Vol 20 (18) ◽  
pp. 2190-2206
Author(s):  
Tasnim Zahan ◽  
Plabon K. Das ◽  
Syeda F. Akter ◽  
Rowshanul Habib ◽  
Md. Habibur Rahman ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Cancer Recurrence ◽  
Therapy Resistance ◽  
Metabolic Reprogramming ◽  
Contributing Factors ◽  
Mesenchymal Transition ◽  
Cellular Processes ◽  
Resistance Property

Background: Chemoresistance is a vital problem in cancer therapy where cancer cells develop mechanisms to encounter the effect of chemotherapeutics, resulting in cancer recurrence. In addition, chemotherapy- resistant leads to the formation of a more aggressive form of cancer cells, which, in turn, contributes to the poor survival of patients with cancer. Objective: In this review, we aimed to provide an overview of how the therapy resistance property evolves in cancer cells, contributing factors and their role in cancer chemoresistance, and exemplified the problems of some available therapies. Methods: The published literature on various electronic databases including, Pubmed, Scopus, Google scholar containing keywords cancer therapy resistance, phenotypic, metabolic and epigenetic factors, were vigorously searched, retrieved and analyzed. Results: Cancer cells have developed a range of cellular processes, including uncontrolled activation of Epithelial- Mesenchymal Transition (EMT), metabolic reprogramming and epigenetic alterations. These cellular processes play significant roles in the generation of therapy resistance. Furthermore, the microenvironment where cancer cells evolve effectively contributes to the process of chemoresistance. In tumour microenvironment immune cells, Mesenchymal Stem Cells (MSCs), endothelial cells and cancer-associated fibroblasts (CAFs) contribute to the maintenance of therapy-resistant phenotype via the secretion of factors that promote resistance to chemotherapy. Conclusion: To conclude, as these factors hinder successful cancer therapies, therapeutic resistance property of cancer cells is a subject of intense research, which in turn could open a new horizon to aim for developing efficient therapies.

scholarly journals MicroRNAs: Their Role in Metabolism, Tumor Microenvironment, and Therapeutic Implications in Head and Neck Squamous Cell Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5604
Author(s):  
Shine-Gwo Shiah ◽  
Sung-Tau Chou ◽  
Jang-Yang Chang
Keyword(s):  
Tumor Microenvironment ◽  
Epithelial Mesenchymal Transition ◽  
Tumor Development ◽  
Cell Communication ◽  
Cell Types ◽  
Metabolic Reprogramming ◽  
Mesenchymal Transition ◽  
Therapeutic Implications ◽  
Rna Molecules ◽  
Non Coding Rna

MicroRNAs (miRNAs) are endogenous small non-coding RNA molecules that negatively regulate gene expression by binding to target mRNAs. Deregulated miRNAs can act as either oncogenic miRNAs or tumor suppressor miRNAs in controlling proliferation, differentiation, apoptosis, metastasis, epithelial–mesenchymal transition, and immune responses, which are all involved in the carcinogenesis process of HNSCC. Recent findings have shown that metabolic reprogramming is an important hallmark of cancer, which is necessary for malignant transformation and tumor development. Some reprogrammed metabolisms are believed to be required for HNSCC against an unfavorable tumor microenvironment (TME). The TME is composed of various cell types embedded in the altered extracellular matrix, among which exosomes, secreted by cancer cells, are one of the most important factors. Tumor-derived exosomes reshape the tumor microenvironment and play a crucial role in cell-to-cell communication during HNSCC development. Exosomes encapsulate many biomolecules, including miRNAs, circulate in body fluids, and can transmit intercellular regulatory messages to nearby and distant sites, which indicates that exosomal miRNAs have the potential to become non-invasive biomarkers. This review aims to clarify the functions of diverse miRNAs in HNSCC metabolic reprogramming and tumor-derived exosomes. In addition, it also emphasizes the potential role of miRNA as a biomarker in the diagnosis, prognosis, and treatment of HNSCC cancer.

scholarly journals Osteopontin Expression in Thyroid Cancer: Deciphering EMT-Related Molecular Mechanisms

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1372
Author(s):  
Bruna Prunes Pena Baroni Viana ◽  
Amanda Vitória Pampolha Gomes ◽  
Etel Rodrigues Pereira Gimba ◽  
Luciana Bueno Ferreira
Keyword(s):  
Thyroid Cancer ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Endocrine System ◽  
Good Prognosis ◽  
Thyroid Tumor ◽  
Diagnostic Tools ◽  
Matricellular Protein ◽  
Mesenchymal Transition

Thyroid cancer is the most common tumor arising from the endocrine system and generally presents good prognosis. However, its aggressive subtypes are related to therapeutic resistance and early metastasis. Epithelial–mesenchymal transition (EMT) and its reverse process, the mesenchymal–epithelial transition (MET), are key events mediating cancer progression, including in thyroid cancer. The matricellular protein osteopontin (OPN) has been reported as a master regulator of EMT in many tumor types. Although high OPN expression has been described and associated with important aspects of thyroid cancer progression, there is no clear evidence regarding OPN as a regulator of EMT in thyroid cancer. Thus, taking together the known roles of OPN in the modulation of EMT in cancer and the information reporting the expression of OPN in thyroid tumor progression, this review aims at summarizing and discussing data related to EMT in thyroid cancer and its putative relation to the roles of OPN in the development of thyroid cancer. These data provide new insights into the molecular mechanisms by which OPN could potentially modulate EMT in thyroid tumors, generating evidence for future studies that may contribute to new therapeutic, prognostic and/or diagnostic tools.

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