scholarly journals Epithelial-to-Mesenchymal Transition in the Light of Plasticity and Hybrid E/M States

2021 ◽  
Vol 10 (11) ◽  
pp. 2403
Author(s):  
Laura Bornes ◽  
Guillaume Belthier ◽  
Jacco van Rheenen
Keyword(s):  
Wound Healing ◽  
Cell Adhesion ◽  
Basement Membrane ◽  
Cell Polarity ◽  
Cancer Progression ◽  
Cancer Metastasis ◽  
Epithelial To Mesenchymal Transition ◽  
Therapy Resistance ◽  
Mesenchymal Transition

Epithelial-to-mesenchymal transition (EMT) is a cellular program which leads to cells losing epithelial features, including cell polarity, cell–cell adhesion and attachment to the basement membrane, while gaining mesenchymal characteristics, such as invasive properties and stemness. This program is involved in embryogenesis, wound healing and cancer progression. Over the years, the role of EMT in cancer progression has been heavily debated, and the requirement of this process in metastasis even has been disputed. In this review, we discuss previous discrepancies in the light of recent findings on EMT, plasticity and hybrid E/M states. Moreover, we highlight various tumor microenvironmental cues and cell intrinsic signaling pathways that induce and sustain EMT programs, plasticity and hybrid E/M states. Lastly, we discuss how recent findings on plasticity, especially on those that enable cells to switch between hybrid E/M states, have changed our understanding on the role of EMT in cancer metastasis, stemness and therapy resistance.

scholarly journals The Role of Cancer-Associated Fibroblasts in Cancer Invasion and Metastasis

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4720
Author(s):  
Paris Jabeen Asif ◽  
Ciro Longobardi ◽  
Michael Hahne ◽  
Jan Paul Medema
Keyword(s):  
Cancer Progression ◽  
Epithelial To Mesenchymal Transition ◽  
Therapy Resistance ◽  
Cancer Invasion ◽  
Cancer Associated Fibroblasts ◽  
Targeted Therapeutics ◽  
Invasion And Metastasis ◽  
Mesenchymal Transition ◽  
Future Studies

Cancer-associated fibroblasts (CAFs) play a key role in cancer progression by contributing to extracellular matrix (ECM) deposition and remodeling, extensive crosstalk with cancer cells, epithelial-to-mesenchymal transition (EMT), invasion, metastasis, and therapy resistance. As metastasis is a main reason for cancer-related deaths, it is crucial to understand the role of CAFs in this process. Colorectal cancer (CRC) is a heterogeneous disease and lethality is especially common in a subtype of CRC with high stromal infiltration. A key component of stroma is cancer-associated fibroblasts (CAFs). To provide new perspectives for research on CAFs and CAF-targeted therapeutics, especially in CRC, we discuss the mechanisms, crosstalk, and functions involved in CAF-mediated cancer invasion, metastasis, and protection. This summary can serve as a framework for future studies elucidating these roles of CAFs.

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 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.

Role of Epithelial-to-Mesenchymal Transition in Inflammatory Bowel Disease

2018 ◽  
Vol 13 (5) ◽  
pp. 659-668 ◽  
Author(s):  
Sara Lovisa ◽  
Giannicola Genovese ◽  
Silvio Danese
Keyword(s):  
Inflammatory Bowel Disease ◽  
Wound Healing ◽  
Bowel Disease ◽  
Molecular Mechanisms ◽  
Epithelial To Mesenchymal Transition ◽  
Clinical Manifestations ◽  
Mesenchymal Transition ◽  
Intestinal Fibrosis ◽  
Inflammatory Bowel

Abstract Intestinal fibrosis is an inevitable complication in patients with inflammatory bowel disease [IBD], occurring in its two major clinical manifestations: ulcerative colitis and Crohn’s disease. Fibrosis represents the final outcome of the host reaction to persistent inflammation, which triggers a prolonged wound healing response resulting in the excessive deposition of extracellular matrix, eventually leading to intestinal dysfunction. The process of epithelial-to-mesenchymal transition [EMT] represents an embryonic program relaunched during wound healing, fibrosis and cancer. Here we discuss the initial observations and the most recent findings highlighting the role of EMT in IBD-associated intestinal fibrosis and fistulae formation. In addition, we briefly review knowledge on the cognate process of endothelial-to-mesenchymal transition [EndMT]. Understanding EMT functionality and the molecular mechanisms underlying the activation of this mesenchymal programme will permit designing new therapeutic strategies to halt the fibrogenic response in the intestine.

The Role of Calcium Signaling in Regulation of Epithelial-Mesenchymal Transition

2020 ◽  
pp. 1-23
Author(s):  
Divya Adiga ◽  
Raghu Radhakrishnan ◽  
Sanjiban Chakrabarty ◽  
Prashant Kumar ◽  
Shama Prasada Kabekkodu
Keyword(s):  
Cancer Metastasis ◽  
Epithelial To Mesenchymal Transition ◽  
Epithelial Mesenchymal Transition ◽  
Critical Role ◽  
Cancer Therapeutics ◽  
Growth And Survival ◽  
Mesenchymal Transition ◽  
Microenvironmental Factors ◽  
Favorable Clinical Outcome

Despite substantial advances in the field of cancer therapeutics, metastasis is a significant challenge for a favorable clinical outcome. Epithelial to mesenchymal transition (EMT) is a process of acquiring increased motility, invasiveness, and therapeutic resistance by cancer cells for their sustained growth and survival. A plethora of intrinsic mechanisms and extrinsic microenvironmental factors drive the process of cancer metastasis. Calcium (Ca<sup>2+</sup>) signaling plays a critical role in dictating the adaptive metastatic cell behavior comprising of cell migration, invasion, angiogenesis, and intravasation. By modulating EMT, Ca<sup>2+</sup> signaling can regulate the complexity and dynamics of events leading to metastasis. This review summarizes the role of Ca<sup>2+</sup> signal remodeling in the regulation of EMT and metastasis in cancer.

scholarly journals Differing Roles of Hyaluronan Molecular Weight on Cancer Cell Behavior and Chemotherapy Resistance

Cancers ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 482 ◽  
Author(s):  
Zoe Price ◽  
Noor Lokman ◽  
Carmela Ricciardelli
Keyword(s):  
Molecular Weight ◽  
Tyrosine Kinase ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Receptor Tyrosine Kinase ◽  
Intracellular Signaling ◽  
Therapy Resistance ◽  
Cell Behavior ◽  
Mesenchymal Transition

Hyaluronan (HA), a glycosaminoglycan located in the extracellular matrix, is important in embryo development, inflammation, wound healing and cancer. There is an extensive body of research demonstrating the role of HA in all stages of cancer, from initiation to relapse and therapy resistance. HA interacts with multiple cell surface receptors, including CD44, receptor for hyaluronan mediated motility (RHAMM) and intracellular signaling pathways, including receptor tyrosine kinase pathways, to promote the survival and proliferation of cancer cells. Additionally, HA promotes the formation of cancer stem cell (CSC) populations, which are hypothesized to be responsible for the initiation of tumors and therapy resistance. Recent studies have identified that the molecular weight of HA plays differing roles on both normal and cancer cell behavior. This review explores the role of HA in cancer progression and therapy resistance and how its molecular weight is important in regulating CSC populations, epithelial to mesenchymal transition (EMT), ATP binding cassette (ABC) transporter expression and receptor tyrosine kinase pathways.

scholarly journals Extracellular HSP90α-LRP1 Signaling Promote Pancreatic Cancer Metastasis and Chemoresistance Via Regulating Epithelial-To-Mesenchymal Transition

2021 ◽  
Author(s):  
Nina Xue ◽  
Tingting Du ◽  
Fangfang Lai ◽  
Jing Jin ◽  
Ming Ji ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Metastasis ◽  
Epithelial To Mesenchymal Transition ◽  
Epithelial Mesenchymal Transition ◽  
Critical Role ◽  
Density Lipoprotein ◽  
Underlying Mechanism ◽  
Migration And Invasion ◽  
Mesenchymal Transition

Abstract Extracellular heat shock protein 90α (HSP90α) has been reported to promote cancer cell invasion and migration. However, whether pancreatic cancer (PC) cells expressed membrane-bound or secreted HSP90α and its underlying mechanism for PC progression were still unclear. Our study pointed out that highly invasive Capan2 cells has a higher level of secreted HSP90α, rather than membrane HSP90α, compared with those of less invasive PL45 cells. The conditioned medium of Capan2 cells or recombinant HSP90α protein was able to stimulate the migration and invasion of PL45 or capan2 cells, which could be prevented by a neutralizing anti-HSP90α antibody. Furthermore, secreted HSP90α promoted elements of epithelial-mesenchymal transition (EMT) in PL45 cells, including increases in vimentin and snail expressions, decreases in E-cadherin expression and changes in cell shape towards a mesenchymal phenotype, but these phenomena were reversed by anti-HSP90α antibody in Capan2 cells. In addition, high levels of low-density lipoprotein receptor-related protein 1 (LRP1) mRNA were associated with worsened patient survival in pancreatic adenocarcinoma. LRP1 as a receptor of eHSP90α for its stimulatory role of PC cells EMT and metastasis by activating AKT signaling. Down-regulation of LRP1 could promote chemosensitivity to gemcitabine and doxorubicin, but not to topotecan and paclitaxel in Capan2 cells. Therefore, our study reveals a critical role of secreted HSP90α on EMT events and suggests blocking secreted HSP90α underlies an aspect of metastasis and chemoresistance.

scholarly journals Enhanced osteopontin splicing regulated by RUNX2 is HDAC-dependent and induces invasive phenotypes in NSCLC cells

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Jing Huang ◽  
Siyuan Chang ◽  
Yabin Lu ◽  
Jing Wang ◽  
Yang Si ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Cancer Metastasis ◽  
Epithelial To Mesenchymal Transition ◽  
A549 Cells ◽  
Gene Promoter ◽  
Nsclc Cell Line ◽  
Dependent Manner ◽  
Mesenchymal Transition ◽  
Splicing Variant ◽  
Splicing Isoforms

Abstract Background Increased cell mobility is a signature when tumor cells undergo epithelial-to-mesenchymal transition. TGF-β is a key stimulating factor to promote the transcription of a variety of downstream genes to accelerate cancer progression and metastasis, including osteopontin (OPN) which exists in several functional forms as different splicing variants. In non-small cell lung cancer cells, although increased total OPN expression was observed under various EMT conditions, the exact constitution and the underlining mechanism towards the generation of such OPN splicing isoforms was poorly understood. Methods We investigated the possible mechanisms of osteopontin splicing variant and its role in EMT and cancer metastasis using NSCLC cell line and cell and molecular biology techniques. Results In this study, we determined that OPNc, an exon 4 excluded shorter form of Opn gene products, appeared to be more potent to promote cell invasion. The expression of OPNc was selectively increased to higher abundance during EMT following TGF-β induction. The switching from OPNa to OPNc could be enhanced by RUNX2 (a transcription factor that recognizes the Opn gene promoter) overexpression, but appeared to be strictly in a HDAC dependent manner in A549 cells. The results suggested the increase of minor splicing variant of OPNc required both (1) the enhanced transcription from its coding gene driven by specific transcription factors; and (2) the simultaneous modulation or fluctuation of the coupled splicing process that depends to selective classed of epigenetic regulators, predominately HDAC family members. Conclusion Our study not only emphasized the importance of splicing variant for its role in EMT and cancer metastasis, but also helped to understand the possible mechanisms of the epigenetic controls for defining the levels and kinetic of gene splicing isoforms and their generations.

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