Downregulation of E-cadherin in pluripotent stem cells triggers partial EMT

Abán, Cyntia; Lombardi, Antonella; Neiman, Gabriel; Biani, M. C.; Greca, Alejandro La; Waisman, Ariel; Moro, Lucía; Sevlever, Gustavo; Miriuka, Santiago Gabriel; Luzzani, Carlos

doi:10.1038/s41598-021-81735-1

Cited by 61 publications

(31 citation statements)

References 32 publications

(38 reference statements)

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“…Metastasis is one of the key molecular steps affecting the prognosis of advanced GC patients. And Epithelial-mesenchymal transition (EMT) is one of the important steps in the process related to metastasis in gastric cancer ( Valastyan and Weinberg, 2011 ).EMT refers to the phenomenon that epithelial cells transform into mesenchymal cells under specific physiological and pathological condition ( Aban et al, 2021 ). And it can down-regulate the epithelial markers E-cadherin, ZO-1, etc., which can inhibite the characteristics and behavior of epithelial cells.…”

Section: E-cadherinmentioning

confidence: 99%

“…The decrease of E-cadherin expression on the cell membrane leads to weakening or disappearance of the interaction between cells and inhibit the activation of transcription factors (Snail, Slug, Twist and ZEB-1), resulting in EMT ( Kalluri and Weinberg, 2009 ; Aban et al, 2021 ). Studies have found that Snail family transcription factors are strong repressors of E-cadherin gene transcription.…”

Section: E-cadherinmentioning

confidence: 99%

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Overview on the Role of E-Cadherin in Gastric Cancer: Dysregulation and Clinical Implications

Zhao

Chen

et al. 2021

Front. Mol. Biosci.

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Gastric cancer is the fifth most common cancer and the third most common cause of cancer death all over the world. E-cadherin encoded by human CDH1 gene plays important roles in tumorigenesis as well as in tumor progression, invasion and metastasis. Full-length E-cadhrin tethered on the cell membrane mainly mediates adherens junctions between cells and is involved in maintaining the normal structure of epithelial tissues. After proteolysis, the extracellular fragment of the full-length E-cadhein is released into the extracellular environment and the blood, which is called soluble E-cadherin (sE-cadherin). sE-cadherin promots invasion and metastasis as a paracrine/autocrine signaling molecule in the progression of various types of cancer including gastric cancer. This review mainly summarizes the dysregulation of E-cadherin and the regulatory roles in the progression, invasion, metastasis, and drug-resistance, as well as its clinical applications in diagnosis, prognosis, and therapeutics of gastric cancer.

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Section: E-cadherinmentioning

confidence: 99%

Section: E-cadherinmentioning

confidence: 99%

Overview on the Role of E-Cadherin in Gastric Cancer: Dysregulation and Clinical Implications

Zhao

Chen

et al. 2021

Front. Mol. Biosci.

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“…Moreover, to move to the correct position to conduct sub-population differentiation, the progenitor cells can modulate the E-cadherin to upregulate SNAIL1/2 resulting in partial EMT [ 214 ]. The expression of SNAIL1 can serve as an EMT hallmark in cell biology, especially in cancer progression.…”

Section: Defined Emt Molecules In Cancermentioning

confidence: 99%

Stationed or Relocating: The Seesawing EMT/MET Determinants from Embryonic Development to Cancer Metastasis

Hsu

Chang

et al. 2021

Biomedicines

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Epithelial and mesenchymal transition mechanisms continue to occur during the cell cycle and throughout human development from the embryo stage to death. In embryo development, epithelial-mesenchymal transition (EMT) can be divided into three essential steps. First, endoderm, mesoderm, and neural crest cells form, then the cells are subdivided, and finally, cardiac valve formation occurs. After the embryonic period, the human body will be subjected to ongoing mechanical stress or injury. The formation of a wound requires EMT to recruit fibroblasts to generate granulation tissues, repair the wound and re-create an intact skin barrier. However, once cells transform into a malignant tumor, the tumor cells acquire the characteristic of immortality. Local cell growth with no growth inhibition creates a solid tumor. If the tumor cannot obtain enough nutrition in situ, the tumor cells will undergo EMT and invade the basal membrane of nearby blood vessels. The tumor cells are transported through the bloodstream to secondary sites and then begin to form colonies and undergo reverse EMT, the so-called “mesenchymal-epithelial transition (MET).” This dynamic change involves cell morphology, environmental conditions, and external stimuli. Therefore, in this manuscript, the similarities and differences between EMT and MET will be dissected from embryonic development to the stage of cancer metastasis.

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“…Even though downregulation of E-cadherin has been shown to induce EMT independently in some cancer models ( 16 , 17 ), a study carried out by Vafaizadeh and her colleagues ( 18 ) suggests that active β-catenin is essential for invasion in culture and experimental metastasis model attributed in part to detachment of adherens junctions during early EMT and subsequent degradation. Deducing in tandem with their structural arrangement, the implication of these findings is that β-catenin acts cooperatively with E-cadherin to initiate EMT ( Figure 2 ), suggesting that β-catenin may be an important therapeutic target in certain types of cancer.…”

Section: Emt and Metastasismentioning

confidence: 99%

Understanding the Complex Milieu of Epithelial-Mesenchymal Transition in Cancer Metastasis: New Insight Into the Roles of Transcription Factors

et al. 2021

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Epithelial-mesenchymal transition (EMT) is a physiological program during which polarised, immobile epithelial cells lose connection with their neighbours and are converted to migratory mesenchymal phenotype. Mechanistically, EMT occurs via a series of genetic and cellular events leading to the repression of epithelial-associated markers and upregulation of mesenchymal-associated markers. EMT is very crucial for many biological processes such as embryogenesis and ontogenesis during human development, and again it plays a significant role in wound healing during a programmed replacement of the damaged tissues. However, this process is often hijacked in pathological conditions such as tumour metastasis, which constitutes the most significant drawback in the fight against cancer, accounting for about 90% of cancer-associated mortality globally. Worse still, metastatic tumours are not only challenging to treat with the available conventional radiotherapy and surgical interventions but also resistant to several cytotoxic agents during treatment, owing to their anatomically diffuse localisation in the body system. As the quest to find an effective method of addressing metastasis in cancer intervention heightens, understanding the molecular interplay involving the signalling pathways, downstream effectors, and their interactions with the EMT would be an important requisite while the challenges of metastasis continue to punctuate. Unfortunately, the molecular underpinnings that govern this process remain to be completely illuminated. However, it is becoming increasingly clear that EMT, which initiates every episode of metastasis, significantly requires some master regulators called EMT transcription factors (EMT-TFs). Thus, this review critically examines the roles of TFs as drivers of molecular rewiring that lead to tumour initiation, progression, EMT, metastasis, and colonisation. In addition, it discusses the interaction of various signalling molecules and effector proteins with these factors. It also provides insight into promising therapeutic targets that may inhibit the metastatic process to overcome the limitation of “undruggable” cancer targets in therapeutic design and upturn the current spate of drug resistance. More so, it extends the discussion from the basic understanding of the EMT binary switch model, and ultimately unveiling the E/M cellular plasticity along a phenotypic spectrum via multiple trans-differentiations. It wraps up on how this knowledge update shapes the diagnostic and clinical approaches that may demand a potential shift in investigative paradigm using novel technologies such as single-cell analyses to improve overall patient survival.

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Downregulation of E-cadherin in pluripotent stem cells triggers partial EMT

Cited by 61 publications

References 32 publications

Overview on the Role of E-Cadherin in Gastric Cancer: Dysregulation and Clinical Implications

Overview on the Role of E-Cadherin in Gastric Cancer: Dysregulation and Clinical Implications

Stationed or Relocating: The Seesawing EMT/MET Determinants from Embryonic Development to Cancer Metastasis

Understanding the Complex Milieu of Epithelial-Mesenchymal Transition in Cancer Metastasis: New Insight Into the Roles of Transcription Factors

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