Distinct interactions between epithelial and mesenchymal cells control cell morphology and collective migration during sponge epithelial to mesenchymal transition

2019 ◽  
Vol 281 (2) ◽  
pp. 183-195
Author(s):  
Manoel L. Costa ◽  
Ivone Andrade Rosa ◽  
Leonardo Andrade ◽  
Claudia Mermelstein ◽  
Cristiano C. Coutinho
Keyword(s):  
Cell Morphology ◽  
Epithelial To Mesenchymal Transition ◽  
Control Cell ◽  
Mesenchymal Cells ◽  
Collective Migration ◽  
Mesenchymal Transition

scholarly journals Evidence for and against epithelial-to-mesenchymal transition in the liver

2013 ◽  
Vol 305 (12) ◽  
pp. G881-G890 ◽  
Author(s):  
Guanhua Xie ◽  
Anna Mae Diehl
Keyword(s):  
Liver Injury ◽  
Epithelial Cells ◽  
Hepatic Stellate Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Stellate Cell ◽  
Stellate Cells ◽  
Mesenchymal Cells ◽  
Mesenchymal Transition ◽  
Liver Epithelial Cells ◽  
Liver Repair

The outcome of liver injury is determined by the success of repair. Liver repair involves replacement of damaged liver tissue with healthy liver epithelial cells (including both hepatocytes and cholangiocytes) and reconstruction of normal liver structure and function. Current dogma posits that replication of surviving mature hepatocytes and cholangiocytes drives the regeneration of liver epithelium after injury, whereas failure of liver repair commonly leads to fibrosis, a scarring condition in which hepatic stellate cells, the main liver-resident mesenchymal cells, play the major role. The present review discusses other mechanisms that might be responsible for the regeneration of new liver epithelial cells and outgrowth of matrix-producing mesenchymal cells during hepatic injury. This theory proposes that, during liver injury, some epithelial cells undergo epithelial-to-mesenchymal transition (EMT), acquire myofibroblastic phenotypes/features, and contribute to fibrogenesis, whereas certain mesenchymal cells (namely hepatic stellate cells and stellate cell-derived myofibroblasts) undergo mesenchymal-to-epithelial transition (MET), revert to epithelial cells, and ultimately differentiate into either hepatocytes or cholangiocytes. Although this theory is highly controversial, it suggests that the balance between EMT and MET modulates the outcome of liver injury. This review summarizes recent advances that support or refute the concept that certain types of liver cells are capable of phenotype transition (i.e., EMT and MET) during both culture conditions and chronic liver injury.

scholarly journals Organoid and Primary Epithelial Cultures of Human Prostate Show the Key Role of the Epithelial-to-Mesenchymal Transition in Generation of Tissue-Specific Stromal Cells

2021 ◽  
Author(s):  
V. M. Ryabov ◽  
A. O. Georgieva ◽  
M. A. Voskresensky ◽  
B. K. Komyakov ◽  
O. V. Rogoza ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Epithelial Cells ◽  
Stromal Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Mesenchymal Cells ◽  
Spontaneous Transformation ◽  
Homogeneous Population ◽  
Tissue Specific ◽  
Mesenchymal Transition ◽  
Organoid Cultures

Abstract The prostate gland (PG) is a small organ in the male reproductive system that is currently the focus of biomedical research due to its leading position in morbidity and mortality from the tissue-specific prostate cancer (PC). The PG epithelium, which undergoes a cancerous transformation, is formed and functions under the control of androgens. At the beginning of the disease, epithelial cells produce an androgen receptor (AR) and are sensitive to androgen-deprivation therapy. However, such therapy inevitably leads to the transition of the disease to the castration-resistant prostate cancer (CRPC), which manifests itself in metastasis and rapid mortality. In CRPC, the cells of the prostate epithelium change their phenotype, that may be associated with AR mutation and loss the sensitivity to specific therapy. The mechanism of PG phenotypic transformation may be hidden in the interaction and formation of the stromal and epithelial cells, which are evident during the establishment of the primary cultures. The aim of this study was to investigate the generation of human PG stromal cells in primary stromal and organoid cultures. We found that, in contrast to the rapid appearance and formation of a homogeneous population of mesenchymal cells in primary stromal cultures of most tissues, human PG cell cultures are formed initially from epithelial cells. They appear in the second week of cultivation and produce cytokeratins (CKs). A homogeneous population of mesenchymal cells producing vimentin is formed only at the end of the fourth week of cultivation. It is accompanied by the disappearance of epithelial cells. At the same time, some epithelial cells simultaneously produce CKs and vimentin. In PG organoid cultures, there is often a concomitant growth of epithelial, but not mesenchymal, cells on culture plastic. During the cultivation of epithelial cells arising from the organoid cultures, they, like the cells of the primary epithelium, exhibit the ability to spontaneous transformation into mesenchymal cells and simultaneously produce CKs and vimentin. Our data suggest that in primary and organoid PG cultures, stromal cells can be formed from epithelium due to the epithelial-to-mesenchymal transition (EMT). The tendency of PG epithelium toward spontaneous EMT may contribute to the mechanism of high sensitivity of prostate tissue to malignant transformation and metastasis. Understanding this mechanism may contribute to the development of effective antitumor therapy of prostate cancer.

scholarly journals Ectoderm to mesoderm transition by down-regulation of actomyosin contractility

PLoS Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
pp. e3001060
Author(s):  
Leily Kashkooli ◽  
David Rozema ◽  
Lina Espejo-Ramirez ◽  
Paul Lasko ◽  
François Fagotto
Keyword(s):  
Epithelial To Mesenchymal Transition ◽  
Specific Property ◽  
Tissue Level ◽  
Small Gtpase ◽  
Collective Migration ◽  
Down Regulation ◽  
Mesenchymal Transition ◽  
Cortical Tension ◽  
Actomyosin Contractility ◽  
Rock Inhibition

Collective migration of cohesive tissues is a fundamental process in morphogenesis and is particularly well illustrated during gastrulation by the rapid and massive internalization of the mesoderm, which contrasts with the much more modest movements of the ectoderm. In the Xenopus embryo, the differences in morphogenetic capabilities of ectoderm and mesoderm can be connected to the intrinsic motility of individual cells, very low for ectoderm, highly for mesoderm. Surprisingly, we find that these seemingly deep differences can be accounted for simply by differences in Rho-kinases (Rock)-dependent actomyosin contractility. We show that Rock inhibition is sufficient to rapidly unleash motility in the ectoderm and confer it with mesoderm-like properties. In the mesoderm, this motility is dependent on 2 negative regulators of RhoA, the small GTPase Rnd1 and the RhoGAP Shirin/Dlc2/ArhGAP37. Both are absolutely essential for gastrulation. At the cellular and tissue level, the 2 regulators show overlapping yet distinct functions. They both contribute to decrease cortical tension and confer motility, but Shirin tends to increase tissue fluidity and stimulate dispersion, while Rnd1 tends to favor more compact collective migration. Thus, each is able to contribute to a specific property of the migratory behavior of the mesoderm. We propose that the “ectoderm to mesoderm transition” is a prototypic case of collective migration driven by a down-regulation of cellular tension, without the need for the complex changes traditionally associated with the epithelial-to-mesenchymal transition.

scholarly journals Epithelial to mesenchymal transition and microRNA expression are associated with spindle and apocrine cell morphology in triple-negative breast cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Marketa Koleckova ◽  
Jiri Ehrmann ◽  
Jan Bouchal ◽  
Maria Janikova ◽  
Aneta Brisudova ◽  
...  
Keyword(s):  
Cell Morphology ◽  
Mirna Expression ◽  
Epithelial To Mesenchymal Transition ◽  
Triple Negative ◽  
Spindle Cell ◽  
Cell Transformation ◽  
Mirna Expression Profile ◽  
Breast Cancers ◽  
Mesenchymal Transition ◽  
Regulated Expression

AbstractTriple negative breast cancers (TNBC) are a morphologically and genetically heterogeneous group of breast cancers with uncertain prediction of biological behavior and response to therapy. Epithelial to mesenchymal transition (EMT) is a dynamic process characterized by loss of typical epithelial phenotype and acquisition of mesenchymal characteristics. Aberrant activation of EMT can aggravate the prognosis of patients with cancer, however, the mechanisms of EMT and role of microRNAs (miRNAs) in EMT activation is still unclear. The aim of our study was to analyze miRNA expression within areas of TNBCs with cellular morphology that may be related to the EMT process and discuss possible associations. Out of all 3953 re-examined breast cancers, 460 breast cancers were diagnosed as TNBC (11.64%). With regard to complete tumor morphology preservation, the tissue samples obtained from core—cut biopsies and influenced by previous neoadjuvant therapy were excluded. We assembled a set of selected 25 cases to determine miRNA expression levels in relation to present focal spindle cell and apocrine cell morphology within individual TNBCs. We used descriptive (histological typing and morphology), morphometric, molecular (microdissection of tumor and non-tumor morphologies, RNA isolation and purification, microchip analysis) and bioinformatic analysis (including pathway analysis). The results were verified by quantitative real-time PCR (RT-qPCR) on an extended set of 70 TNBCs. The majority of TNBCs were represented by high—grade invasive carcinomas of no special type (NST) with medullary features characterized by well-circumscribed tumors with central necrosis or fibrosis and frequent tendency to spindle-cell and/or apocrine cell transformation. Apocrine and spindle cell transformation showed a specific miRNA expression profile in comparison to other tumor parts, in situ carcinoma or non-tumor structures, particularly down-regulated expression of hsa-miRNA-143-3p and hsa-miRNA-205-5p and up-regulated expression of hsa-miR-22-3p, hsa-miRNA-185-5p, and hsa-miR-4443. Apocrine cell tumor morphology further revealed decreased expression of hsa-miR-145-5p and increased expression of additional 14 miRNAs (e.g. hsa-miR-182-5p, hsa-miR-3135b and hsa-miR-4417). Pathway analysis for target genes of these miRNAs revealed several shared biological processes (i.e. Wnt signaling, ErbB signaling, MAPK signaling, endocytosis and axon guidance), which may in part contribute to the EMT and tumor progression. We provide the first miRNA expression profiling of specific tissue morphologies in TNBC. Our results demonstrate a specific miRNA expression profile of apocrine and spindle cell morphology which can exhibit a certain similarity with the EMT process and may also be relevant for prognosis and therapy resistance of TNBC.

scholarly journals Epithelial to mesenchymal transition—The roles of cell morphology, labile adhesion and junctional coupling

2013 ◽  
Vol 111 (2) ◽  
pp. 435-446 ◽  
Author(s):  
Tariq Abdulla ◽  
Luis Luna-Zurita ◽  
José Luis de la Pompa ◽  
Jean-Marc Schleich ◽  
Ron Summers
Keyword(s):  
Cell Morphology ◽  
Epithelial To Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Junctional Coupling

scholarly journals Ectoderm to mesoderm transition by downregulation of actomyosin contractility

2019 ◽  
Author(s):  
Leily Kashkooli ◽  
David Rozema ◽  
Lina Espejo-Ramirez ◽  
Paul Lasko ◽  
François Fagotto
Keyword(s):  
Epithelial To Mesenchymal Transition ◽  
Specific Property ◽  
Tissue Level ◽  
Small Gtpase ◽  
Collective Migration ◽  
Mesenchymal Transition ◽  
Cortical Tension ◽  
Actomyosin Contractility ◽  
Fundamental Process ◽  
Rock Inhibition

SummaryCollective migration of cohesive tissues is a fundamental process in morphogenesis, and is particularly well illustrated during gastrulation by the rapid and massive internalization of the mesoderm, which contrasts with the much more modest movements of the ectoderm. In the Xenopus embryo, the differences in morphogenetic capabilities of ectoderm and mesoderm can be connected to the intrinsic motility of individual cells, very low for ectoderm, highly for mesoderm. Surprisingly, we find these seemingly deep differences can be accounted for simply by differences in Rock-dependent actomyosin contractility. We show that Rock inhibition is sufficient to rapidly unleash motility in the ectoderm and confer it with mesoderm-like properties. In the mesoderm, this motility is dependent on two negative regulators of RhoA, the small GTPase Rnd1 and the RhoGAP Shirin/Dlc2/ArhGAP37. Both are absolutely essential for gastrulation. At the cellular and tissue level, the two regulators show overlapping yet distinct functions. They both contribute to decrease cortical tension and confer motility, but Shirin tends to increase tissue fluidity and stimulate dispersion, while Rnd1 tends to favour more compact collective migration. Thus, each is able to contribute to a specific property of the migratory behaviour of the mesoderm. We propose that the “ectoderm to mesoderm transition” is a prototypic case of collective migration driven by a downregulation of cellular tension, without the need for the complex changes traditionally associated with the epithelial to mesenchymal transition.

scholarly journals The Regulatory Role of MicroRNAs in EMT and Cancer

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Apostolos Zaravinos
Keyword(s):  
Signaling Pathways ◽  
Malignant Transformation ◽  
Epithelial To Mesenchymal Transition ◽  
Control Cell ◽  
Cell Plasticity ◽  
Aberrant Expression ◽  
Mesenchymal Transition ◽  
Cell Architecture ◽  
Recent Developments

The epithelial to mesenchymal transition (EMT) is a powerful process in tumor invasion, metastasis, and tumorigenesis and describes the molecular reprogramming and phenotypic changes that are characterized by a transition from polarized immotile epithelial cells to motile mesenchymal cells. It is now well known that miRNAs are important regulators of malignant transformation and metastasis. The aberrant expression of the miR-200 family in cancer and its involvement in the initiation and progression of malignant transformation has been well demonstrated. The metastasis suppressive role of the miR-200 members is strongly associated with a pathologic EMT. This review describes the most recent advances regarding the influence of miRNAs in EMT and the control they exert in major signaling pathways in various cancers. The ability of the autocrine TGF-β/ZEB/miR-200 signaling regulatory network to control cell plasticity between the epithelial and mesenchymal state is further discussed. Various miRNAs are reported to directly target EMT transcription factors and components of the cell architecture, as well as miRNAs that are able to reverse the EMT process by targeting the Notch and Wnt signaling pathways. The link between cancer stem cells and EMT is also reported and the most recent developments regarding clinical trials that are currently using anti-miRNA constructs are further discussed.

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.

Sign in / Sign up

Export Citation Format

Share Document