Leo - L4

Questions and Answers

What is epithelial to mesenchymal transition (EMT) and its significance in cancer development?

EMT is the process by which epithelial cells acquire mesenchymal characteristics, enabling them to gain motility, which is vital for cancer invasiveness and metastasis.

How do the characteristics of epithelial cells contrast with those of mesenchymal cells?

Epithelial cells have cohesive interactions and a well-organized structure with tight junctions, while mesenchymal cells exhibit weak interactions, lack organization, and are not polarized.

Why are epithelial cells considered stable and not motile under normal conditions?

Epithelial cells are tightly packed and linked by tight junctions, which restricts their mobility and maintains the integrity of tissue layers.

What physiological roles does EMT play during normal development?

During normal development, EMT facilitates the formation of various tissues and organs by allowing epithelial cells to migrate and differentiate into mesenchymal cells. Signup and view all the answers

In the context of cancer, what does it mean for epithelial cells to acquire motility?

Acquiring motility allows cancerous epithelial cells to detach from the primary tumor and migrate to distant sites, which is essential for metastasis. Signup and view all the answers

Describe the consequences of mesenchymal cells not being polarized.

The lack of polarization in mesenchymal cells means they do not have clearly defined membrane domains, resulting in reduced structural organization and functionality. Signup and view all the answers

What role do tight junctions play in the behavior of epithelial cells?

Tight junctions create strong adhesive interactions between epithelial cells, enabling them to form a continuous layer and preventing mobility. Signup and view all the answers

What distinguishes mesenchymal cells from epithelial cells in terms of cell adhesion?

Mesenchymal cells do not adhere closely to one another and lack tight junctions, while epithelial cells adhere through E-cadherin and desmosomes. Signup and view all the answers

How does the presence of vimentin serve as a marker for mesenchymal cells?

Vimentin is an intermediate filament highly expressed in mesenchymal cells, indicating their identity as opposed to epithelial cells, which express E-cadherin. Signup and view all the answers

Explain the significance of epithelial to mesenchymal transition (EMT).

EMT is significant as it allows epithelial cells to change their phenotype to a mesenchymal type, enhancing their motility and invasive capabilities. Signup and view all the answers

What role does E-cadherin play in epithelial cells compared to mesenchymal cells?

E-cadherin is critical for cell adhesion in epithelial cells but is reduced and sequestered inside vesicles in mesenchymal cells. Signup and view all the answers

Describe the changes in cell-cell junctions that occur before EMT.

Before EMT, epithelial cells undergo dissolution of their cell-to-cell junctions, which leads to reduced cellular adhesion and loss of apical-basal polarity. Signup and view all the answers

What are the main transcription factors involved in the downregulation of E-cadherin during EMT?

The main transcription factors are SNAIL and TWIST. Signup and view all the answers

What are the three polarity complexes responsible for the organization in epithelial cells?

The three polarity complexes are the Scribble complex, Crumbs complex, and Par complex. Signup and view all the answers

How do genetic mutations contribute to the reduction of E-cadherin expression in cancer cells?

Genetic mutations can lead to an incorrect synthesis of E-cadherins, resulting in their defective function or degradation. Signup and view all the answers

What happens to mesenchymal cells that undergo mesenchymal to epithelial transition (MET)?

Mesenchymal cells that undergo MET revert to an epithelial phenotype, restoring their adhesion and polarity. Signup and view all the answers

What role does N-cadherin play in the progression of cancer cells undergoing EMT?

N-cadherin promotes cell-death resistance and enhances the invasiveness of cancer cells. Signup and view all the answers

How do tight junctions differ between mesenchymal and epithelial cells?

Tight junctions are present and functional in epithelial cells providing strong adhesion, while they are absent in mesenchymal cells. Signup and view all the answers

What effect do growth factors like VEGF and HGF have on the EMT process?

VEGF and HGF promote EMT by inducing expression of SNAIL and increasing N-cadherin while decreasing E-cadherin. Signup and view all the answers

What is the role of the basement membrane in epithelial cell organization?

The basement membrane provides structural support and facilitates stable adhesion for epithelial cells, contributing to their organized layer. Signup and view all the answers

What epigenetic changes can lead to the silencing of the E-cadherin gene in carcinomas?

Hypermethylation and post transcriptional modifications can silence the E-cadherin gene. Signup and view all the answers

What is the significance of E-cadherin decrease during the epithelial to mesenchymal transition (EMT) process?

The decrease in E-cadherin is crucial as it reduces cell-cell adhesion, allowing epithelial cells to acquire motility and facilitating the EMT process. Signup and view all the answers

How does the expression of polarity complexes like Scribble change during EMT?

The decreased expression of E-cadherin leads to reduced interaction of the Scribble polarity complex with the plasma membrane, weakening cell adhesion. Signup and view all the answers

What morphological changes occur in epithelial cells as they undergo EMT?

Epithelial cells transition to a more globular shape, resembling mesenchymal cells, enabling greater motility. Signup and view all the answers

Explain the role of EMT in normal developmental processes.

EMT is essential for the differentiation and organization of specialized tissues and organ systems during embryonic development. Signup and view all the answers

What is the relationship between EMT and cancer invasiveness?

EMT enhances cancer cell motility, enabling malignant cells to detach, migrate, and form metastases in secondary locations. Signup and view all the answers

What does MET stand for and how does it relate to EMT?

MET stands for mesenchymal to epithelial transition; it is a reversible process allowing mesenchymal cells to regain epithelial traits. Signup and view all the answers

List some physiological processes influenced by EMT.

EMT is involved in neural crest formation, heart morphogenesis, and wound healing. Signup and view all the answers

How do ectopic expressions of cadherins impact EMT?

Increased expression of alternative cadherins like N-cadherin helps in the transition to mesenchymal phenotypes during EMT. Signup and view all the answers

What are the essential cellular mechanisms activated for cancer cells to migrate?

Cancer cells activate differentiation genes, reduce proliferation, and engage anti-apoptotic mechanisms to enable migration. Signup and view all the answers

Describe the role of EMT in pathological conditions.

In pathological conditions, EMT contributes to fibrosis and cancer progression, particularly in epithelial tumors, by promoting cell motility. Signup and view all the answers

What is the significance of down-regulating receptors in cancer cell migration?

Down-regulating receptors reduces cell-to-cell interactions, facilitating the dissolution of tight junctions necessary for cell migration. Signup and view all the answers

How does changing the phenotype from epithelial to mesenchymal potentially benefit cancer cells?

This phenotypic change allows cancer cells to acquire greater motility and invasiveness, essential for metastasis. Signup and view all the answers

Why do cancer cells need to activate proteases during the EMT process?

Activating proteases enables degradation of the extracellular matrix, which is necessary for cancer cells to migrate and invade new areas. Signup and view all the answers

What distinguishes pathological EMT from physiological EMT in terms of regulation?

Pathological EMT occurs in an irregular and time-independent manner, lacking the tight spatial and temporal regulation seen in physiological EMT. Signup and view all the answers

Describe the role of tumor heterogeneity in the EMT process.

Tumor heterogeneity leads to varying responses among different cell populations, resulting in asynchronous EMT and metastasis capabilities. Signup and view all the answers

How do genetic and epigenetic changes collectively influence the EMT process?

Both genetic and epigenetic changes are necessary for EMT, as genetic changes provide irreversible mutations while epigenetic changes modulate gene expression in a reversible manner. Signup and view all the answers

Why is it important for cancerous cells to reduce their proliferation during the EMT process?

Reducing proliferation facilitates the transition to a motile mesenchymal phenotype, allowing cells to migrate and invade effectively. Signup and view all the answers

What factors may lead to bypassing certain events during the EMT process in cancer?

Oncogenic pathways driven by growth factors and molecules may alter the sequence and timing of events in EMT, leading to bypassing regulatory checkpoints. Signup and view all the answers

In the context of tumor progression, what happens to the organization and shape of the cells during EMT?

Cells lose their organized apico-basal polarity and adopt a more irregular shape, enhancing their ability to invade and migrate. Signup and view all the answers

What role do metalloproteins play in cancer cell migration?

Metalloproteins degrade components of the extracellular matrix, enabling cancer cells to pass through and migrate more freely. Signup and view all the answers

Study Notes

Epithelial to Mesenchymal Transition (EMT)

EMT allows stable epithelial cells to acquire motility by transitioning to a mesenchymal phenotype.
It occurs during normal tissue development and is critical in cancer progression, facilitating invasiveness and metastasis formation.
Malignant epithelial cells detach from the primary tumor to spread and form secondary tumors.

Epithelial Cells

Characterized by cohesive interactions forming continuous layers with three membrane domains: apical, lateral, and basal.
Tight junctions and protein E-cadherin are crucial for cell adhesion and organization.
Epithelial cells exhibit apico-basal polarization of organelles and cytoskeletal components, restricting their mobility.

Mesenchymal Cells

Lack tight junctions, leading to weak or absent intercellular adhesion, allowing mobility within the extracellular matrix.
Do not show typical epithelial polarization and are organized differently with vimentin as a specific marker.
Vimentin filaments are present near the plasma membrane, contrasting with low levels found in epithelial cells.

EMT Process

Involves a regulated switch from epithelial to mesenchymal phenotype, with the potential for reversal (MET).
Changes in cell-cell junctions are necessary for EMT, including the dissolution of tight junctions and downregulation of E-cadherin.
Reduced E-cadherin expression leads to decreased cell adhesion and increased motility, crucial for cancer invasiveness.

Role of Polarity Complexes

Polarity complexes (Scribble, Crumbs, Par) maintain epithelial cell organization and attachment.
Loss of E-cadherin disrupts these complexes, fostering a less stable, motile mesenchymal phenotype.

Normal Development Involvement

EMT is essential during embryonic development, leading to the formation of organs and tissues.
Key events include the generation of germ layers during gastrulation and differentiation processes.
Normal physiological processes such as wound healing also involve EMT.

Pathological EMT

EMT contributes to conditions like fibrosis and cancer, particularly in epithelial cancers.
Cancer cells must adopt a mesenchymal phenotype to migrate, necessitating gene activation for differentiation and reduced proliferation.
Steps in cancer cell migration include degrading cell-to-cell junctions and altering cell adhesion properties.

Breast Cancer Specifics

EMT in breast cancer is critical for transitioning from non-invasive carcinoma in situ to invasive ductal carcinoma.
Loss of epithelial characteristics and increased motility promote metastasis.

Differences Between Physiological and Pathological EMT

Physiological EMT occurs in a regulated manner, while pathological EMT may follow an irregular progression.
Tumor heterogeneity affects the timing and success of EMT among cancer cells; not all cells experience EMT simultaneously or successfully metastasize.

Genetic and Epigenetic Changes

EMT and MET are influenced by both genetic mutations and reversible epigenetic changes, highlighting the complexity of cancer development and metastasis.### Epigenetic Changes in EMT
Epigenetic changes are reversible modifications of DNA status, maintaining the DNA sequence.
Key forms of epigenetic changes include histone modifications, DNA methylation, and alterations in microRNAs (miRNAs).

Key Oncogenes in Epithelial-Mesenchymal Transition (EMT)

SNAIL, TWIST, and ZEB are critical oncogenes involved in EMT, responsible for promoting tumor invasiveness and metastasis.
These oncogenes downregulate epithelial markers (e.g., E-cadherin) and upregulate mesenchymal markers (e.g., N-cadherin, vimentin).
The downregulation of E-cadherin is a crucial early step in EMT, leading to tumor cell invasiveness.

Functional Role of E-cadherin

E-cadherin prevents tumor cell migration by maintaining cell-to-cell adhesion, acting as a tumor suppressor.
Loss of E-cadherin function due to genetic mutations or epigenetic changes facilitates cancer progression.

Additional Factors Influencing EMT

Growth factors, such as FGF1, HGF, IGF1, EGF, and VEGF, can promote EMT by affecting E-cadherin and N-cadherin levels and activating SNAIL and TWIST oncogenes.
These factors can induce changes that impact the extracellular matrix, facilitating tumor cell movement.

Process of EMT and Metastasis Formation

EMT allows epithelial tumor cells to transition to a mesenchymal phenotype, enabling mobility and invasion.
Key steps include loss of tight junctions, increased motility through matrix degradation, and blood/lymphatic dissemination.
Successful metastasis requires the reacquisition of the epithelial phenotype through the MET process after establishing in a secondary site.

Transition from EMT to MET

MET is essential for secondary tumor formation, requiring the downregulation of mesenchymal markers and upregulation of epithelial markers.
The reversal from mesenchymal to epithelial state restores cell adhesion capabilities, crucial for metastasis success.

Epigenetic Mechanisms and Their Roles

Reversible epigenetic mechanisms rather than irreversible genetic mutations mediate EMT and MET processes.
Common modifications include histone acetylation (gene activation) and DNA methylation (gene repression).
miRNAs play a pivotal role in regulating the expression of oncogenes involved in EMT and MET, with specific miRNAs targeting SNAIL, TWIST, and ZEB.

Functional Implications of miRNAs

MiRNA-200 inhibits ZEB, while miRNA-34 and miRNA-203 inhibit SNAIL, collectively promoting MET.
The regulation of specific miRNAs is crucial to the reversal of EMT and the facilitation of MET.

Consequences of Impaired MET

Cells that cannot revert to an epithelial phenotype due to mutations may fail to establish successful metastasis, highlighting the importance of MET in cancer progression.

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Description

This quiz explores the process of epithelial to mesenchymal transition, detailing its significance in tissue development and cancer progression. Understand how malignant cells acquire motility and influence metastasis through this critical transition. Gain insights into the characteristics of epithelial and mesenchymal cells and their differences.