Welcome to our blog article on Epithelial-Mesenchymal Transition (EMT), skin, cancer, cellular signaling, and the potential impact of resveratrol!
Epithelial-mesenchymal transition (EMT) is an important biological process that allows epithelial cells to take on a more migratory mesenchymal phenotype. While EMT is crucial for normal development and wound healing, dysregulated EMT can drive cancer progression and metastasis. The natural compound resveratrol has recently emerged as a potent modulator of EMT signaling.
In this blog article, we explore the biology of EMT and its implications in cancer. We spotlight research demonstrating resveratrol’s ability to inhibit aberrant EMT in various cancer models. Through modulating key cell signaling pathways, resveratrol shows promise in suppressing EMT-mediated cancer invasion and metastasis.
We delve into resveratrol’s potential EMT-modulating effects in skin health and skin cancer. We also touch on other phytonutrients under study for targeting dysregulated EMT in cancer. Understanding resveratrol’s mechanisms of action could open new avenues for nutrition-based approaches to managing EMT-driven diseases.
Join us as we unravel the connections between EMT, cellular signaling, and natural compounds like resveratrol. We aim to highlight cutting-edge research on leveraging food-derived compounds to control EMT and associated pathologies. Read on to learn more about nature’s gems that may one day aid EMT-related conditions.
Basic Definitions
Here are simplified definitions of the key concepts:
Epithelial:
- Cells that line cavities and surfaces in the body like skin and organs
- Tightly packed, organized structure with cell-cell junctions
- Polarized with distinct apical and basal sides
Mesenchymal:
- Loose, unstructured cells like fibroblasts and smooth muscle cells
- Mobile, can migrate to other parts of the body
- Lack polarity and cell-cell junctions
EMT (Epithelial-Mesenchymal Transition):
- Process where epithelial cells lose their characteristics and gain mesenchymal properties
- Cells detach from organized epithelial layers and become mobile
- Important in development, wound healing, and cancer metastasis
In summary, EMT involves a transition from structured epithelial cells to loose mesenchymal cells. This allows cell migration during normal processes like embryonic development, however dysregulated EMT can promote cancer invasion and metastasis.
More on Epithelial-Mesenchymal Transition (EMT)
Epithelial-Mesenchymal Transition (EMT) is a cellular process through which epithelial cells undergo a series of changes to acquire a mesenchymal phenotype. EMT is characterized by the loss of cell-cell adhesion molecules, such as E-cadherin, and the gain of mesenchymal markers, such as vimentin and N-cadherin. This transition is driven by the activation of specific EMT transcription factors that play a crucial role in regulating gene expression and promoting the phenotypic changes associated with EMT.
EMT is a dynamic process that occurs during various physiological and pathological conditions, including embryonic development, tissue remodeling, wound healing, and cancer metastasis. In development, EMT is essential for the formation of various tissues and organs, as it allows for the migration and invasion of cells to their target locations.
In wound healing, EMT facilitates the migration of epithelial cells to the site of injury, promoting tissue repair. However, EMT dysregulation has been implicated in cancer progression and metastasis, where cancer cells acquire invasive properties and the ability to spread to distant sites.
“Epithelial-mesenchymal transitions (EMTs), the acquisition of mesenchymal features from epithelial cells, occur during some biological processes and are classified into three types: the first type occurs during embryonic development, the second type is associated with adult tissue regeneration, and the third type occurs in cancer progression. EMT occurring during embryonic development in gastrulation, renal development, and the origin and fate of the neural crest is a highly regulated process, while EMT occurring during tumor progression s highly deregulated.” (Ribatti 2020)
EMT markers, such as E-cadherin, vimentin, and N-cadherin, are widely used to assess the occurrence of EMT in cells and tissues. Additionally, various EMT transcription factors, including Snail, Twist, and ZEB1, have been identified as key regulators of EMT. These transcription factors bind to specific DNA sequences, known as EMT regulatory elements, and modulate the expression of genes involved in epithelial maintenance and mesenchymal conversion.
Understanding the molecular mechanisms underlying EMT is crucial for unraveling its role in development, tissue repair, and disease progression. Researchers continue to investigate the intricate signaling pathways and transcriptional networks that drive EMT, with the aim of developing targeted therapies to modulate EMT in disease contexts, such as cancer.
What is Snail-mediated EMT (Epithelial-Mesenchymal Transition) signaling
Snail-mediated EMT (Epithelial-Mesenchymal Transition) signaling is a crucial process in cellular biology that involves the regulation of EMT by the Snail transcription factor. Snail belongs to the Snail family of zinc finger proteins and plays a pivotal role in repressing E-cadherin, a key protein responsible for cell-cell adhesion.
During Snail-mediated EMT, epithelial cells undergo a series of molecular changes that result in the loss of their epithelial characteristics and the acquisition of mesenchymal properties. This includes the downregulation of epithelial markers, such as E-cadherin, and the upregulation of mesenchymal markers, such as N-cadherin and vimentin.
Snail achieves these effects by disrupting the E-cadherin complex and inhibiting its expression. This loss of cell-cell adhesion allows the epithelial cells to dissociate from their neighbors and acquire a more migratory and invasive phenotype, characteristics often associated with mesenchymal cells.
The Snail transcription factor is part of a complex network of EMT signaling pathways that interact with other transcription factors, signaling molecules, and microRNAs to tightly regulate the process. These pathways include the TGF-β, Wnt/β-catenin, Notch, and JAK/STAT pathways, among others. Together, these signaling pathways orchestrate the dynamic cellular changes required for EMT and are essential for normal development, wound healing, and tissue regeneration.
Understanding the intricate mechanisms of Snail-mediated EMT signaling is crucial for unraveling the role of EMT in various physiological and pathological processes, including embryogenesis, tissue fibrosis, organogenesis, and cancer metastasis. Advances in this field have the potential to open new avenues for therapeutic interventions targeting EMT-related diseases.
“Several transcription factors, including the Snail/Slug family, Twist, δEF1/ZEB1, SIP1/ZEB2 and E12/E47 respond to microenvironmental stimuli and function as molecular switches for the EMT program. Snail is a zinc-finger transcriptional repressor controlling EMT during embryogenesis and tumor progression. Through its N-terminal SNAG domain, Snail interacts with several corepressors and epigenetic remodeling complexes to repress specific target genes, such as the E-cadherin gene (CDH1). An integrated and complex signaling network, including the RTKs, TGF-β, Notch, Wnt, TNF-α, and BMPs pathways, activates Snail, thereby inducing EMT.” (Wang 2013)
EMT and Cancer
Epithelial-Mesenchymal Transition (EMT) plays a crucial role in cancer progression and metastasis. During this process, cancer cells undergo molecular and phenotypic changes, transforming from an epithelial state to a mesenchymal state. This transition enables cancer cells to acquire enhanced migratory and invasive properties, enabling them to penetrate surrounding tissues and spread to distant sites.
EMT is driven by various molecular factors and signaling pathways, leading to the loss of cell-cell adhesion molecules like E-cadherin and the gain of mesenchymal markers. Understanding the mechanisms behind EMT in cancer can provide valuable insights into tumor development and metastatic dissemination.
To illustrate the significance of EMT in cancer, imagine a scenario where tumor cells maintain an epithelial phenotype. These cells would be confined to the primary tumor site and would not possess the ability to invade surrounding tissues or spread to distant organs.
However, through EMT, cancer cells acquire the ability to break free from the primary tumor and invade neighboring tissues, facilitating the initiation of metastatic colonization in secondary sites. This process significantly contributes to the aggressiveness and poor prognosis of many cancer types.
EMT is not an absolute requirement for metastasis, but can certainly facilitate invasion and dispersion of tumors.
“There have been several signaling pathways found to be associated with the induction of the EMT process in cancer cells. Phytoestrogens were demonstrated to have chemopreventive effects on cancer metastasis by inhibiting EMT-associated pathways, such as Notch-1 and TGF-beta signaling. As a result, phytoestrogens can inhibit or reverse the EMT process by upregulating the expression of epithelial phenotypes, including E-cadherin, and downregulating the expression of mesenchymal phenotypes, including N-cadherin, Snail, Slug, and vimentin. In this review, we focused on the important roles of phytoestrogens in inhibiting EMT in many types of cancer and suggested phytoestrogens as prominent alternative compounds to chemotherapy.” (Lee 2016)
EMT and Resveratrol
Resveratrol, a natural compound found in grapes, berries, and other plants, has been extensively studied for its potential effects on Epithelial-Mesenchymal Transition (EMT). EMT is a cellular process that plays a crucial role in tissue repair, organ formation, and cancer metastasis. The ability of resveratrol to modulate EMT has attracted significant interest in the field of skin health and cancer research.
“There is a link between anti-functional plasticity (EMT, CSC, metabolism), pro-apoptosis and modulation of the p53 signaling pathway in CRC cell oncogenesis as one of the main resveratrol mechanisms to suppress or reverse the malignant phenotype, cell migration ability and resistance to conventional drugs in vitro and in vivo, suggesting a great therapeutic importance.” (Brockmueller 2024)
Now of course Resveratol is also an NRF2 Activator, but this dynamic may not be a straightforward as it sounds given uncontrolled NRF2 activity is also associated with troublesome tumor growth. See here for more!
Resveratrol and the skin
The use of resveratrol in skincare products has gained popularity due to its potential benefits for the skin. Studies have suggested that resveratrol exhibits antioxidant and anti-inflammatory properties, which can help protect the skin from oxidative stress and reduce inflammation. These properties make resveratrol a promising ingredient for improving skin health and maintaining a youthful appearance.
“It has been shown that formulations with resveratrol can stimulate the proliferation of fibroblasts and contributing to the increase in the concentration of collagen III. Resveratrol has an affinity for the estrogen protein receptors (both ERα and ERβ), thereby contributing to the stimulation of collagen types I and II production. Moreover, resveratrol also has the antioxidant properties, thus can protect cells against oxidative damage associated with the effects of free radicals and UV radiation on the skin by reducing the expression of AP-1 and NF-kB factors and it slows down the process of photoaging of the skin.” (Ratz-Lyko 2019)
“Resveratrol is now being increasingly employed in cosmetology and dermatology. This polyphenolic phytoalexin is abundantly present in red grapes and berries has a number of scientifically proven health promoting properties. Its popularity in cosmetology and dermatology is primarily associated with proven ability to penetrate the skin barrier and its antiaging activity. Resveratrol has an affinity for the estrogen protein receptors (both ERα and ERβ), thereby contributing to the stimulation of collagen types I and II production.” (Rispo 2023)
Resveratol and Skin Cancer
Emerging research has also explored the potential of resveratrol in preventing and treating skin cancer. Skin cancer, including melanoma and non-melanoma types, is one of the most common forms of cancer worldwide. Resveratrol has been found to possess anti-carcinogenic properties, including the ability to inhibit cancer cell growth, induce apoptosis (programmed cell death), and inhibit angiogenesis (formation of new blood vessels that support tumor growth).
Moreover, resveratrol has been shown to modulate various signaling pathways involved in skin cancer development, such as the Wnt/β-catenin pathway, which plays a crucial role in cancer initiation and progression. By targeting these pathways, resveratrol has the potential to function as a chemopreventive agent against skin cancer.
“Resveratrol could inhibit the proliferation, migration and invasion of skin squamous cell carcinoma cells, which may be related to the up-regulation of miR-126 to inhibit the Wnt / β-catenin signaling pathway.” (Zhang 2020 )
While more research is needed to fully understand the mechanisms and potential therapeutic applications of resveratrol, current studies suggest that it holds promise in enhancing skin health and potentially preventing or treating skin cancer.
EMT and Other Phytonutrients
While resveratrol has received significant attention for its potential effects on epithelial-mesenchymal transition (EMT) and cancer progression, there are other phytonutrients that have also been investigated for their impact on these processes.
Phytonutrients, also known as plant compounds, have been found to possess various beneficial properties, including antioxidant, anti-inflammatory, and anticancer effects. These compounds are abundant in fruits, vegetables, herbs, and spices, making them an essential part of a healthy diet.
Some studies have suggested that certain phytonutrients may have the ability to interfere with EMT, thereby reducing the invasiveness and metastatic potential of cancer cells. For example, curcumin, a compound found in turmeric, has shown promising results in inhibiting EMT and suppressing tumor growth in preclinical studies.
“Collectively, curcumin inhibits ERK- and JNK-mediated EMT through upregulating TFPI-2, which in turn suppresses the migration and invasion of PC cells. These findings provide new insights into the antitumor mechanism of curcumin.” (Zhai 2023)
Additionally, green tea extract, which contains catechins, has been shown to inhibit EMT-related signaling pathways in certain cancer cell lines. These findings open up exciting avenues for further research into the potential role of phytonutrients in modulating EMT and improving not only cancer outcomes, but also other conditions such as lung fibrosis.
“EG (Epigallocatechin gallate, a natural polyphenol extracted from green tea) could improve PM2.5-induced lung fibrosis by decreasing oxidative damage and EMT through AKT/mTOR pathway, which might be a potential candidate for the treatment of PM2.5-induced lung fibrosis.” (Zhongyin 2022)
Sulforaphane from broccoli is another phytonutrient studied for EMT/cancer effects.
“A set of experiments showed that sulforaphase inhibited hepatocellular carcinoma cell migration and invasion, inhibited the formation of fibroblast like mesenchymal cells and the expression of Vimentin, but increased the expression of E-cadherin, suggesting sulforaphane suppresses epithelial-mesenchymal transition (EMT) process.” (Wu 2016)
IMPORTANT
This is an informational page only. Whilst based on recent scientific research, it should not be seen as medical advice. Please consult your medical practitioner in regard to any medical treatment issues.
FAQ
What is Epithelial-Mesenchymal Transition (EMT)?
Epithelial-Mesenchymal Transition (EMT) is a biological process where epithelial cells undergo a series of changes to acquire a mesenchymal phenotype. This process involves the loss of cell-cell adhesion molecules, such as E-cadherin, and the gain of mesenchymal markers, such as vimentin and N-cadherin.
What are the EMT markers and transcription factors?
EMT markers include proteins such as E-cadherin, vimentin, and N-cadherin, which are characteristic of epithelial and mesenchymal cells. Transcription factors such as Snail, Twist, and ZEB1 play key roles in regulating the EMT process.
How does Snail-mediated EMT signaling work?
Snail is a transcription factor that plays a crucial role in the regulation of EMT. It represses the expression of E-cadherin, a cell-cell adhesion molecule. Snail-mediated EMT signaling leads to the acquisition of mesenchymal properties by epithelial cells.
What is the role of EMT in cancer?
EMT plays a crucial role in cancer progression and metastasis. During the epithelial-mesenchymal transition, cancer cells acquire enhanced migratory and invasive properties, allowing them to invade surrounding tissues and spread to distant sites.
What is the relationship between EMT and resveratrol?
Resveratrol, a natural compound found in grapes, berries, and other plants, has been studied for its potential effects on EMT. Research suggests that resveratrol may inhibit EMT process and potentially have beneficial effects in the context of skin health and skin cancer.
How does resveratrol impact the skin?
Studies have shown that resveratrol exhibits antioxidant and anti-inflammatory properties, which may protect the skin from damage caused by environmental factors. Resveratrol also has the potential to modulate EMT and inhibit cancer cell invasion in skin cancer.
Does resveratrol have any effects on skin cancer?
Research suggests that resveratrol may have anti-cancer properties and could potentially inhibit the progression of skin cancer. It has been shown to suppress the migration and invasion of cancer cells, potentially reducing the metastatic potential of skin cancer.
Are there other phytonutrients that have an impact on EMT and cancer?
Apart from resveratrol, other phytonutrients have been investigated for their potential effects on EMT and cancer progression. These include compounds such as curcumin, green tea catechins, and quercetin, which have shown promising results in preclinical studies.