scholarly journals Wnt Signaling in Ovarian Cancer Stemness, EMT, and Therapy Resistance

2019 ◽  
Vol 8 (10) ◽  
pp. 1658 ◽  
Author(s):  
Teeuwssen ◽  
Fodde
Keyword(s):  
Ovarian Cancer ◽  
Wnt Signaling ◽  
Epithelial To Mesenchymal Transition ◽  
Current Knowledge ◽  
Treatment Options ◽  
Chemotherapy Resistance ◽  
Therapy Resistance ◽  
Cancer Stemness ◽  
Mesenchymal Transition

Ovarian cancers represent the deadliest among gynecologic malignancies and are characterized by a hierarchical structure with cancer stem cells (CSCs) endowed with self-renewal and the capacity to differentiate. The Wnt/β-catenin signaling pathway, known to regulate stemness in a broad spectrum of stem cell niches including the ovary, is thought to play an important role in ovarian cancer. Importantly, Wnt activity was shown to correlate with grade, epithelial to mesenchymal transition, chemotherapy resistance, and poor prognosis in ovarian cancer. This review will discuss the current knowledge of the role of Wnt signaling in ovarian cancer stemness, epithelial to mesenchymal transition (EMT), and therapy resistance. In addition, the alleged role of exosomes in the paracrine activation of Wnt signaling and pre-metastatic niche formation will be reviewed. Finally, novel potential treatment options based on Wnt inhibition will be highlighted.

scholarly journals The Role of Epithelial-to-Mesenchymal Plasticity in Ovarian Cancer Progression and Therapy Resistance

Cancers ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 838 ◽  
Author(s):  
Nele Loret ◽  
Hannelore Denys ◽  
Philippe Tummers ◽  
Geert Berx
Keyword(s):  
Ovarian Cancer ◽  
Cell Fate ◽  
Cancer Progression ◽  
Epithelial To Mesenchymal Transition ◽  
Chemotherapy Resistance ◽  
Therapy Resistance ◽  
Cancer Resistance ◽  
Mesenchymal Transition ◽  
Development Of Resistance ◽  
Cancer Cell Survival

Ovarian cancer is the most lethal of all gynecologic malignancies and the eighth leading cause of cancer-related deaths among women worldwide. The main reasons for this poor prognosis are late diagnosis; when the disease is already in an advanced stage, and the frequent development of resistance to current chemotherapeutic regimens. Growing evidence demonstrates that apart from its role in ovarian cancer progression, epithelial-to-mesenchymal transition (EMT) can promote chemotherapy resistance. In this review, we will highlight the contribution of EMT to the distinct steps of ovarian cancer progression. In addition, we will review the different types of ovarian cancer resistance to therapy with particular attention to EMT-mediated mechanisms such as cell fate transitions, enhancement of cancer cell survival, and upregulation of genes related to drug resistance. Preclinical studies of anti-EMT therapies have yielded promising results. However, before anti-EMT therapies can be effectively implemented in clinical trials, more research is needed to elucidate the mechanisms leading to EMT-induced therapy resistance.

scholarly journals Malignant Ascites in Ovarian Cancer: Cellular, Acellular, and Biophysical Determinants of Molecular Characteristics and Therapy Response

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4318
Author(s):  
Brittany P. Rickard ◽  
Christina Conrad ◽  
Aaron J. Sorrin ◽  
Mustafa Kemal Ruhi ◽  
Jocelyn C. Reader ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Biology ◽  
Metastatic Cancer ◽  
Treatment Options ◽  
Therapy Response ◽  
Therapy Resistance ◽  
Malignant Ascites ◽  
Molecular Characteristics ◽  
The Impact

Ascites refers to the abnormal accumulation of fluid in the peritoneum resulting from an underlying pathology, such as metastatic cancer. Among all cancers, advanced-stage epithelial ovarian cancer is most frequently associated with the production of malignant ascites and is the leading cause of death from gynecologic malignancies. Despite decades of evidence showing that the accumulation of peritoneal fluid portends the poorest outcomes for cancer patients, the role of malignant ascites in promoting metastasis and therapy resistance remains poorly understood. This review summarizes the current understanding of malignant ascites, with a focus on ovarian cancer. The first section provides an overview of heterogeneity in ovarian cancer and the pathophysiology of malignant ascites. Next, analytical methods used to characterize the cellular and acellular components of malignant ascites, as well the role of these components in modulating cell biology, are discussed. The review then provides a perspective on the pressures and forces that tumors are subjected to in the presence of malignant ascites and the impact of physical stress on therapy resistance. Treatment options for malignant ascites, including surgical, pharmacological and photochemical interventions are then discussed to highlight challenges and opportunities at the interface of drug discovery, device development and physical sciences in oncology.

scholarly journals Tight junction proteins in gastrointestinal and liver disease

Gut ◽  
2018 ◽  
Vol 68 (3) ◽  
pp. 547-561 ◽  
Author(s):  
Mirjam B Zeisel ◽  
Punita Dhawan ◽  
Thomas F Baumert
Keyword(s):  
Liver Disease ◽  
Tight Junction ◽  
Functional Role ◽  
Epithelial To Mesenchymal Transition ◽  
Current Knowledge ◽  
Regulation Of Gene Expression ◽  
Causative Role ◽  
Mesenchymal Transition ◽  
Disease Biology

Over the past two decades a growing body of evidence has demonstrated an important role of tight junction (TJ) proteins in the physiology and disease biology of GI and liver disease. On one side, TJ proteins exert their functional role as integral proteins of TJs in forming barriers in the gut and the liver. Furthermore, TJ proteins can also be expressed outside TJs where they play important functional roles in signalling, trafficking and regulation of gene expression. A hallmark of TJ proteins in disease biology is their functional role in epithelial-to-mesenchymal transition. A causative role of TJ proteins has been established in the pathogenesis of colorectal cancer and gastric cancer. Among the best characterised roles of TJ proteins in liver disease biology is their function as cell entry receptors for HCV—one of the most common causes of hepatocellular carcinoma. At the same time TJ proteins are emerging as targets for novel therapeutic approaches for GI and liver disease. Here we review our current knowledge of the role of TJ proteins in the pathogenesis of GI and liver disease biology and discuss their potential as therapeutic targets.

Abstract 1873: The role of p21-activated kinase 4 (PAK4) in cancer stemness and epithelial-to-mesenchymal transition

2016 ◽  
Author(s):  
Asfar S. Azmi ◽  
Irfana Muqbil ◽  
Amro Aboukameel ◽  
William Senapedis ◽  
Erkan Baloglu ◽  
...  
Keyword(s):  
Epithelial To Mesenchymal Transition ◽  
Cancer Stemness ◽  
Mesenchymal Transition ◽  
P21 Activated Kinase

scholarly journals Molecular profiling supports the role of epithelial-to-mesenchymal transition (EMT) in ovarian cancer metastasis

2013 ◽  
Vol 6 (1) ◽  
pp. 49 ◽  
Author(s):  
Loukia N Lili ◽  
Lilya V Matyunina ◽  
L Walker ◽  
Stephen L Wells ◽  
Benedict B Benigno ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Metastasis ◽  
Epithelial To Mesenchymal Transition ◽  
Molecular Profiling ◽  
Mesenchymal Transition

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.

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 Exosome-Mediated Signaling in Epithelial to Mesenchymal Transition and Tumor Progression

2018 ◽  
Vol 8 (1) ◽  
pp. 26 ◽  
Author(s):  
Alice Conigliaro ◽  
Carla Cicchini
Keyword(s):  
Tumor Progression ◽  
Intercellular Communication ◽  
Epithelial To Mesenchymal Transition ◽  
Current Knowledge ◽  
Cell Communication ◽  
Therapeutic Approaches ◽  
Mesenchymal Transition ◽  
Rna Molecules ◽  
Dna And Rna

Growing evidence points to exosomes as key mediators of cell–cell communication, by transferring their specific cargo (e.g., proteins, lipids, DNA and RNA molecules) from producing to receiving cells. In cancer, the regulation of the exosome-mediated intercellular communication may be reshaped, inducing relevant changes in gene expression of recipient cells in addition to microenvironment alterations. Notably, exosomes may deliver signals able to induce the transdifferentiation process known as Epithelial-to-Mesenchymal Transition (EMT). In this review, we summarize recent findings on the role of exosomes in tumor progression and EMT, highlighting current knowledge on exosome-mediated intercellular communication in tumor-niche establishment, migration, invasion, and metastasis processes. This body of evidence suggests the relevance of taking into account exosome-mediated signaling and its multifaceted aspects to develop innovative anti-tumoral therapeutic approaches.

scholarly journals Epicardial TGFβ and BMP Signaling in Cardiac Regeneration: What Lesson Can We Learn from the Developing Heart?

Biomolecules ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 404
Author(s):  
Esther Dronkers ◽  
Manon M. M. Wauters ◽  
Marie José Goumans ◽  
Anke M. Smits
Keyword(s):  
Epithelial To Mesenchymal Transition ◽  
Transforming Growth Factor ◽  
Current Knowledge ◽  
Transforming Growth Factor Β ◽  
Heart Tissue ◽  
Vital Role ◽  
Bmp Signaling ◽  
Mesenchymal Transition ◽  
Starting Point

The epicardium, the outer layer of the heart, has been of interest in cardiac research due to its vital role in the developing and diseased heart. During development, epicardial cells are active and supply cells and paracrine cues to the myocardium. In the injured adult heart, the epicardium is re-activated and recapitulates embryonic behavior that is essential for a proper repair response. Two indispensable processes for epicardial contribution to heart tissue formation are epithelial to mesenchymal transition (EMT), and tissue invasion. One of the key groups of cytokines regulating both EMT and invasion is the transforming growth factor β (TGFβ) family, including TGFβ and Bone Morphogenetic Protein (BMP). Abundant research has been performed to understand the role of TGFβ family signaling in the developing epicardium. However, less is known about signaling in the adult epicardium. This review provides an overview of the current knowledge on the role of TGFβ in epicardial behavior both in the development and in the repair of the heart. We aim to describe the presence of involved ligands and receptors to establish if and when signaling can occur. Finally, we discuss potential targets to improve the epicardial contribution to cardiac repair as a starting point for future investigation.

Sign in / Sign up

Export Citation Format

Share Document