scholarly journals EMT-Inducing Molecular Factors in Gynecological Cancers

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Loredana Campo ◽  
Catherine Zhang ◽  
Eun-Kyoung Breuer
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Signs And Symptoms ◽  
Therapeutic Interventions ◽  
Gynecologic Cancers ◽  
Papilloma Virus ◽  
Mesenchymal Transition ◽  
Metastatic Relapse ◽  
Immunodeficiency Virus ◽  
Common Risk Factors ◽  
Molecular Aberrations

Gynecologic cancers are the unregulated growth of neoplastic cells that arise in the cervix, ovaries, fallopian tubes, uterus, vagina, and vulva. Although gynecologic cancers are characterized by different signs and symptoms, studies have shown that they share common risk factors, such as smoking, obesity, age, exposure to certain chemicals, infection with human immunodeficiency virus (HIV), and infection with human papilloma virus (HPV). Despite recent advancements in the preventative, diagnostic, and therapeutic interventions for gynecologic cancers, many patients still die as a result of metastasis and recurrence. Since mounting evidence indicates that the epithelial-mesenchymal transition (EMT) process plays an essential role in metastatic relapse of cancer, understanding the molecular aberrations responsible for the EMT and its underlying signaling should be given high priority in order to reduce cancer morbidity and mortality.

Analysis of DIP2C as a novel regulator for epithelial-mesenchymal transition of rheumatoid arthritis synovium and a potential therapeutic target

Impact ◽  
2021 ◽  
Vol 2021 (8) ◽  
pp. 28-30
Author(s):  
Masao Tanaka
Keyword(s):  
Rheumatoid Arthritis ◽  
Therapeutic Target ◽  
Epithelial Mesenchymal Transition ◽  
Poor Response ◽  
Associate Professor ◽  
Therapeutic Interventions ◽  
Response To Treatment ◽  
Potential Therapeutic Target ◽  
Mesenchymal Transition ◽  
Long Time

Rheumatoid arthritis (RA) is an autoimmune disease that can cause damage to the joints, cartilage and bone. There is no cure but early diagnosis can help mitigate damage. Sometimes RA is particularly difficult to treat, for example when the disease took a long time to be diagnosed. Associate Professor Masao Tanaka, Graduate School of Medicine, Kyoto University, Japan, leads a team of researchers working to improve understanding of the causes of poor response to treatment in RA with a long morbidity. The goal is to restore patients' therapeutic responsiveness, thereby improving outcomes. A previous focus for Tanaka was on a protein called FSTL1. He is now exploring DIP2 as a binding molecule for FSTL1. Other important mechanisms Tanaka is exploring are DNA methylation and the mechanisms of carnitine, which has been found to decrease a variety of activation signalling by inhibiting ceramide production in T cells. He and the team are exploring the involvement of these mechanisms in DIP2. In his most recent investigations, Tanaka is exploring DIP2C as a novel regulator for epithelial-mesenchymal transition of RA synovium and a potential therapeutic target. He is focusing on molecules that are expressed in the cells in joints, making the work directly applicable to RA. The team is carrying out a cohort study called KURAMA (Kyoto University Rheumatoid Arthritis Management Alliance) that involves around 2,000 outpatients with RA. Ultimately, Tanaka hopes to identify a reproducible combination of patient conditions and therapeutic interventions that achieve better treatment results for RA patients.

scholarly journals A new paradigm for leprosy diagnosis based on host gene expression

2021 ◽  
Author(s):  
Thyago Leal-Calvo ◽  
Charlotte Avanzi ◽  
Mayara A Mendes ◽  
Andrej Benjak ◽  
Philippe Busso ◽  
...  
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Transcriptional Profiling ◽  
Clinical Manifestations ◽  
Skin Lesions ◽  
Therapeutic Interventions ◽  
Diagnostic Tools ◽  
New Paradigm ◽  
Mesenchymal Transition ◽  
Ido1 Expression ◽  
Leprosy Patients

Transcriptional profiling is a powerful tool to investigate and detect human diseases. In this study, we used bulk RNA-sequencing (RNA-Seq) to compare the transcriptomes in skin lesions of leprosy patients or matched controls affected by other dermal conditions such as granuloma annulare, a confounder for paucibacillary leprosy. We identified five genes capable of accurately distinguishing multibacillary and paucibacillary leprosy from other skin conditions. Indoleamine 2,3-dioxygenase 1 ( IDO1 ) expression alone was highly discriminatory, followed by TLR10, BLK, CD38, and SLAMF7, whereas the HS3ST2 and CD40LG mRNA separated multi- and paucibacillary leprosy. Finally, from the main differentially expressed genes (DEG) and enriched pathways, we conclude that paucibacillary disease is characterized by epithelioid transformation and granuloma formation, with an exacerbated cellular immune response, while multibacillary leprosy features epithelial-mesenchymal transition with phagocytic and lipid biogenesis patterns in the skin. These findings will help catalyze the development of better diagnostic tools and potential host-based therapeutic interventions. Finally, our data may help elucidate host-pathogen interplay driving disease clinical manifestations.

A Comprehensive Review on Crosstalk of Human Papilloma Virus oncoproteins and developmental/self-renewal pathways during the pathogenesis of uterine cervical cancer

2020 ◽  
Vol 20 ◽  
Author(s):  
Afza Ahmad ◽  
Irfan Ahmad Ansari
Keyword(s):  
Cervical Cancer ◽  
Human Papilloma Virus ◽  
Epithelial Mesenchymal Transition ◽  
Wnt Signaling Pathway ◽  
Hpv Infection ◽  
Uterine Cervical Cancer ◽  
Self Renewal ◽  
Papilloma Virus ◽  
Mesenchymal Transition ◽  
E6 And E7

: Cervical cancer, a cancer arising from the uterine cervix has been regarded as the fourth most frequent gynecological malignancy among females worldwide. Epidemiological reports have shown that uterine cervical cancer is a global health issue among womens of specially developing countries and consequently creates an economic and medical burden in the society. The main causative agent of cervical carcinoma is high risk human papilloma virus (HPV 16 and HPV 18). Molecular studies have revealed the expression two viral genes E6 and E7 after HPV infection in the epithelial cells of cervix. These gene products are known to inactivate the major tumor suppressors, p53 and retinoblastoma protein (pRB), respectively. Moreover, the role of self-renewal pathways such as Hedgehog, Notch and Wnt has also been linked with drug resistance in cancer cells and epithelial mesenchymal transition during metastasis in pathogenesis of cervical cancer. Although, the mechanism of interaction of HPV E6 and E7 with each and every component of above described developmental pathways is not elucidated yet, but preliminary reports of their crosstalk have begun to emerge. Understanding the interplay between these oncoproteins and developmental/self-renewal pathways is highly important in terms of designing new and targeted therapeutic approach against cervical cancer. Hence, this review cynosure the carcinogenesis of HPV with the brief description of its virology and also establishes the crosstalk between oncoproteins E6 & E7 and Hedgehog, Notch and Wnt signaling pathway.

scholarly journals Pathophysiology of Lung Disease and Wound Repair in Cystic Fibrosis

2021 ◽  
Vol 28 (1) ◽  
pp. 155-188
Author(s):  
Massimo Conese ◽  
Sante Di Gioia
Keyword(s):  
Cystic Fibrosis ◽  
Lung Disease ◽  
Wound Repair ◽  
Epithelial Mesenchymal Transition ◽  
Therapeutic Interventions ◽  
In Vivo Studies ◽  
Mesenchymal Transition ◽  
Molecular Events

Cystic fibrosis (CF) is an autosomal recessive, life-threatening condition affecting many organs and tissues, the lung disease being the chief cause of morbidity and mortality. Mutations affecting the CF Transmembrane Conductance Regulator (CFTR) gene determine the expression of a dysfunctional protein that, in turn, triggers a pathophysiological cascade, leading to airway epithelium injury and remodeling. In vitro and in vivo studies point to a dysregulated regeneration and wound repair in CF airways, to be traced back to epithelial CFTR lack/dysfunction. Subsequent altered ion/fluid fluxes and/or signaling result in reduced cell migration and proliferation. Furthermore, the epithelial-mesenchymal transition appears to be partially triggered in CF, contributing to wound closure alteration. Finally, we pose our attention to diverse approaches to tackle this defect, discussing the therapeutic role of protease inhibitors, CFTR modulators and mesenchymal stem cells. Although the pathophysiology of wound repair in CF has been disclosed in some mechanisms, further studies are warranted to understand the cellular and molecular events in more details and to better address therapeutic interventions.

scholarly journals TGFβ signaling networks in ovarian cancer progression and plasticity

2021 ◽  
Vol 38 (2) ◽  
pp. 139-161
Author(s):  
Asha Kumari ◽  
Zainab Shonibare ◽  
Mehri Monavarian ◽  
Rebecca C. Arend ◽  
Nam Y. Lee ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Progression ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Chemotherapy Resistance ◽  
Transforming Growth Factor Β ◽  
Cell Types ◽  
Cell Junctions ◽  
Therapeutic Interventions ◽  
Mesenchymal Transition

AbstractEpithelial ovarian cancer (EOC) is a leading cause of cancer-related death in women. Late-stage diagnosis with significant tumor burden, accompanied by recurrence and chemotherapy resistance, contributes to this poor prognosis. These morbidities are known to be tied to events associated with epithelial-mesenchymal transition (EMT) in cancer. During EMT, localized tumor cells alter their polarity, cell–cell junctions, cell–matrix interactions, acquire motility and invasiveness and an exaggerated potential for metastatic spread. Key triggers for EMT include the Transforming Growth Factor-β (TGFβ) family of growth factors which are actively produced by a wide array of cell types within a specific tumor and metastatic environment. Although TGFβ can act as either a tumor suppressor or promoter in cancer, TGFβ exhibits its pro-tumorigenic functions at least in part via EMT. TGFβ regulates EMT both at the transcriptional and post-transcriptional levels as outlined here. Despite recent advances in TGFβ based therapeutics, limited progress has been seen for ovarian cancers that are in much need of new therapeutic strategies. Here, we summarize and discuss several recent insights into the underlying signaling mechanisms of the TGFβ isoforms in EMT in the unique metastatic environment of EOCs and the current therapeutic interventions that may be relevant.

scholarly journals Transactivation of SOX5 by Brachyury promotes breast cancer bone metastasis

2019 ◽  
Vol 41 (5) ◽  
pp. 551-560 ◽  
Author(s):  
Ming Chen ◽  
Shitao Zou ◽  
Chao He ◽  
Jundong Zhou ◽  
Suoyuan Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Metastasis ◽  
Cancer Progression ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Breast Cancer Patients ◽  
Mesenchymal Transition ◽  
Cancer Aggressiveness ◽  
Metastatic Relapse

Abstract The bone marrow has been long known to host a unique environment amenable to colonization by metastasizing tumor cells. Yet, the underlying molecular interactions which give rise to the high incidence of bone metastasis (BM) in breast cancer patients have long remained uncharacterized. In our study, in vitro and in vivo assays demonstrated that Brachyury (Bry) could promote breast cancer BM. Bry drives epithelial–mesenchymal transition (EMT) and promotes breast cancer aggressiveness. As an EMT driver, SOX5 involves in breast cancer metastasis and the specific function in BM. Chromatin immunoprecipitation (ChIP) assays revealed SOX5 is a direct downstream target gene of Bry. ChIP analysis and reporter assays identified two Bry-binding motifs; one consistent with the classic conserved binding sequence and the other a new motif sequence. This study demonstrates for the first time that Bry promotes breast cancer cells BM through activating SOX5. In clinical practice, targeting the Bry-Sox5-EMT pathway is evolving into a promising avenue for the prevention of bone metastatic relapse, therapeutic resistance and other aspects of breast cancer progression. Brachyury directly regulates the expression of SOX5 by binding to two motifs in its promoter region. The Bry-SOX5-EMT pathway may represent a potential target to develop treatments to prevent and treat bone metastasis from breast cancer.

scholarly journals Mucosal Epithelial Jak Kinases in Health and Diseases

2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Narendra Kumar ◽  
Longxiang Kuang ◽  
Ryan Villa ◽  
Priyam Kumar ◽  
Jayshree Mishra
Keyword(s):  
Immune Cells ◽  
Wound Repair ◽  
Epithelial Mesenchymal Transition ◽  
Transplant Rejection ◽  
Severe Combined Immunodeficiency ◽  
Organ Transplant ◽  
Therapeutic Interventions ◽  
Cell Physiology ◽  
Mesenchymal Transition ◽  
Epithelial Cancers

Janus kinases (Jaks) are a family of nonreceptor tyrosine kinase that include four different members, viz., Jak1, Jak2, Jak3, and Tyk2. Jaks play critical roles in immune cells functions; however, recent studies suggest they also play essential roles in nonimmune cell physiology. This review highlights the significance of epithelial Jaks in understanding the molecular basis of some of the diseases through regulation of epithelial-mesenchymal transition, cell survival, cell growth, development, and differentiation. Growth factors and cytokines produced by the cells of hematopoietic origin use Jak kinases for signal transduction in both immune and nonimmune cells. Among Jaks, Jak3 is widely expressed in both immune cells and in intestinal epithelial cells (IECs) of both humans and mice. Mutations that abrogate Jak3 functions cause an autosomal severe combined immunodeficiency disease (SCID) while activating Jak3 mutations lead to the development of hematologic and epithelial cancers. A selective Jak3 inhibitor CP-690550 (Xeljanz) approved by the FDA for certain chronic inflammatory conditions demonstrates immunosuppressive activity in rheumatoid arthritis, psoriasis, and organ transplant rejection. Here, we also focus on the consequences of Jak3-directed drugs on adverse effects in light of recent discoveries in mucosal epithelial functions of Jak3 with some information on other Jaks. Lastly, we brief on structural implications of Jak3 domains beyond the immune cells. As information about the roles of Jak3 in gastrointestinal functions and associated diseases are only just emerging, in the review, we summarize its implications in gastrointestinal wound repair, inflammatory bowel disease, obesity-associated metabolic syndrome, and epithelial cancers. Lastly, we shed lights on identifying potential novel targets in developing therapeutic interventions of diseases associated with dysfunctional IEC.

scholarly journals Mesenchymal Characteristics and Predictive Biomarkers on Circulating Tumor Cells for Therapeutic Strategy

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3588
Author(s):  
Takahiro Okabe ◽  
Shinsaku Togo ◽  
Yuichi Fujimoto ◽  
Junko Watanabe ◽  
Issei Sumiyoshi ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Therapeutic Strategy ◽  
Epithelial Mesenchymal Transition ◽  
Predictive Biomarkers ◽  
Metastatic Potential ◽  
Tumor Stem Cell ◽  
Mesenchymal Transition ◽  
Metastatic Relapse

Metastasis-related events are the primary cause of cancer-related deaths, and circulating tumor cells (CTCs) have a pivotal role in metastatic relapse. CTCs include a variety of subtypes with different functional characteristics. Interestingly, the epithelial–mesenchymal transition (EMT) markers expressed in CTCs are strongly associated with poor clinical outcome and related to the acquisition of circulating tumor stem cell (CTSC) features. Recent studies have revealed the existence of CTC clusters, also called circulating tumor microemboli (CTM), which have a high metastatic potential. In this review, we present current opinions regarding the clinical significance of CTCs and CTM with a mesenchymal phenotype as clinical surrogate markers, and we summarize the therapeutic strategy according to phenotype characterization of CTCs in various types of cancers for future precision medicine.

scholarly journals EMTome: a resource for pan-cancer analysis of epithelial-mesenchymal transition genes and signatures

2020 ◽  
Vol 124 (1) ◽  
pp. 259-269
Author(s):  
Suhas V. Vasaikar ◽  
Abhijeet P. Deshmukh ◽  
Petra den Hollander ◽  
Sridevi Addanki ◽  
Nick Allen Kuburich ◽  
...  
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Primary Tumour ◽  
The Cancer Genome Atlas ◽  
Therapeutic Interventions ◽  
Metastatic Tumour ◽  
Tumour Mass ◽  
Web Based ◽  
Mesenchymal Transition ◽  
Gene Signatures ◽  
Cancer Types

Abstract Background The epithelial-mesenchymal transition (EMT) enables dissociation of tumour cells from the primary tumour mass, invasion through the extracellular matrix, intravasation into blood vessels and colonisation of distant organs. Cells that revert to the epithelial state via the mesenchymal-epithelial transition cause metastases, the primary cause of death in cancer patients. EMT also empowers cancer cells with stem-cell properties and induces resistance to chemotherapeutic drugs. Understanding the driving factors of EMT is critical for the development of effective therapeutic interventions. Methods This manuscript describes the generation of a database containing EMT gene signatures derived from cell lines, patient-derived xenografts and patient studies across cancer types and multiomics data and the creation of a web-based portal to provide a comprehensive analysis resource. Results EMTome incorporates (i) EMT gene signatures; (ii) EMT-related genes with multiomics features across different cancer types; (iii) interactomes of EMT-related genes (miRNAs, transcription factors, and proteins); (iv) immune profiles identified from The Cancer Genome Atlas (TCGA) cohorts by exploring transcriptomics, epigenomics, and proteomics, and drug sensitivity and (iv) clinical outcomes of cancer cohorts linked to EMT gene signatures. Conclusion The web-based EMTome portal is a resource for primary and metastatic tumour research publicly available at www.emtome.org.

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