scholarly journals Consequences of EMT-Driven Changes in the Immune Microenvironment of Breast Cancer and Therapeutic Response of Cancer Cells

2019 ◽  
Vol 8 (5) ◽  
pp. 642 ◽  
Author(s):  
Snahlata Singh ◽  
Rumela Chakrabarti
Keyword(s):  
Breast Cancer ◽  
Tumor Progression ◽  
Tumor Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Therapeutic Response ◽  
Current Knowledge ◽  
Cell Contact ◽  
Invasive Potential ◽  
Mesenchymal Transition ◽  
Tumor Growth And Metastasis

Epithelial-to-mesenchymal transition (EMT) is a process through which epithelial cells lose their epithelial characteristics and cell–cell contact, thus increasing their invasive potential. In addition to its well-known roles in embryonic development, wound healing, and regeneration, EMT plays an important role in tumor progression and metastatic invasion. In breast cancer, EMT both increases the migratory capacity and invasive potential of tumor cells, and initiates protumorigenic alterations in the tumor microenvironment (TME). In particular, recent evidence has linked increased expression of EMT markers such as TWIST1 and MMPs in breast tumors with increased immune infiltration in the TME. These immune cells then provide cues that promote immune evasion by tumor cells, which is associated with enhanced tumor progression and metastasis. In the current review, we will summarize the current knowledge of the role of EMT in the biology of different subtypes of breast cancer. We will further explore the correlation between genetic switches leading to EMT and EMT-induced alterations within the TME that drive tumor growth and metastasis, as well as their possible effect on therapeutic response in breast cancer.

scholarly journals Matrix metalloproteinases in the process of invasion and metastasis of breast cancer

2006 ◽  
Vol 14 (3-4) ◽  
pp. 136-140 ◽  
Author(s):  
Gordana Konjevic ◽  
Sandra Stankovic
Keyword(s):  
Breast Cancer ◽  
Matrix Metalloproteinases ◽  
Tumor Progression ◽  
Tumor Cells ◽  
Proteolytic Enzymes ◽  
Tissue Inhibitors Of Metalloproteinases ◽  
Collagen Type Iv ◽  
Cell Contact ◽  
Invasion And Metastasis ◽  
Mesenchymal Transition

Metastatic cascade in malignant tumors, including breast cancer, starts with localized invasion of the host tissue. This process, requiring that tumor cells separate from each other, includes loss of homotypic and heterotypic cell adhesion and cell-cell contact inhibition, acquisition of motility, exacerbated by "epithelial-to-mesenchymal transition", and production of proteolytic enzymes which degrade basal membrane and extracellular matrix. In this sense, aside from urokinase type plasminogen activator, increased expression and activity of matrix metalloproteinases (MMPs) is one of the earliest and most sustained events in tumor progression, playing a role in angiogenesis, invasion and metastasis. MMPs are a family of 23 zinc metalloproteinases, secreted as latent pro-enzymes, activated by proteolytic cleavage, and inhibited by the tissue inhibitors of metalloproteinases. The most commonly connected MMPs with the processes of metastasis are MMP-2 (gelatinase A) and MMP-9 (gelatinase B), due to their ability to degrade collagen type IV, major component of vascular basement membrane. MMP-2 and MMP-9 are also required for the switch to the "angiogenic phenotype" during tumor progression and activation of dormant tumor cells. The association of the increase in serum MMP-2 and MMP-9 activity and clinical stage suggests the usefulness of these parameters as markers in the follow-up and prognosis of breast cancer patients. The concept of "stromal-directed therapy" of cancer, with MMP-inhibitors directed against MMPs as targets, is based on the observed MMP up-regulation in tumors.

scholarly journals Two Faces of TGF-Beta1 in Breast Cancer

2014 ◽  
Vol 2014 ◽  
pp. 1-16 ◽  
Author(s):  
Joanna Magdalena Zarzynska
Keyword(s):  
Breast Cancer ◽  
Cell Cycle Progression ◽  
Epithelial To Mesenchymal Transition ◽  
Current Knowledge ◽  
Clinical Investigation ◽  
Mesenchymal Transition ◽  
Early Stages ◽  
New Therapeutic Approaches ◽  
Genes Encoding ◽  
Life Threatening

Breast cancer (BC) is potentially life-threatening malignancy that still causes high mortality among women. Scientific research in this field is focused on deeper understanding of pathogenesis and progressing of BC, in order to develop relevant diagnosis and improve therapeutic treatment. Multifunctional cytokine TGF-β1 is one of many factors that have a direct influence on BC pathophysiology. Expression of TGF-β1, induction of canonical and noncanonical signaling pathways, and mutations in genes encoding TGF-β1 and its receptors are correlated with oncogenic activity of this cytokine. In early stages of BC this cytokine inhibits epithelial cell cycle progression and promotes apoptosis, showing tumor suppressive effects. However, in late stages, TGF-β1 is linked with increased tumor progression, higher cell motility, cancer invasiveness, and metastasis. It is also involved in cancer microenvironment modification and promotion of epithelial to mesenchymal transition (EMT). This review summarizes the current knowledge on the phenomenon called “TGF-β1 paradox”, showing that better understanding of TGF-β1 functions can be a step towards development of new therapeutic approaches. According to current knowledge several drugs against TGF-β1 have been developed and are either in nonclinical or in early stages of clinical investigation.

scholarly journals The interplay of autophagy and epithelial-to-mesenchymal transition in cancer progression

2020 ◽  
Vol 7 (2) ◽  
pp. 8-19
Author(s):  
O. O. Ryabaya ◽  
A. A. Prokofieva
Keyword(s):  
Tumor Progression ◽  
Cancer Progression ◽  
Epithelial To Mesenchymal Transition ◽  
Current Knowledge ◽  
Biological Processes ◽  
Antitumor Therapy ◽  
Mesenchymal Transition ◽  
New Strategy ◽  
Adverse Environmental Conditions ◽  
The One

Autophagy and epithelial-to-mesenchymal transition (EMT) are the main biological processes involved in tumor progression, and are closely linked. On the one hand, activation of autophagy provides energy and essential nutrients for EMT during the metastases spreading, which is required for tumor cells survival in adverse environmental conditions. On the other hand, autophagy, acting as a tumor suppressor, tends to inhibit metastasis by selectively suppressing the transcription factors of EMT in the early stages. Therefore, inhibition of EMT by inhibitors or inducers of autophagy may be a new strategy for antitumor therapy. Thus, the aim of this review is to highlight current knowledge about the crosstalk between autophagy and EMT processes in tumor progression and to summarize data supporting the necessity of parallel regulation of two processes through signaling pathways.

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