Fibroblast growth factors and their receptors in cancer

2011 ◽  
Vol 437 (2) ◽  
pp. 199-213 ◽  
Author(s):  
Jørgen Wesche ◽  
Kaisa Haglund ◽  
Ellen Margrethe Haugsten
Keyword(s):  
Growth Factors ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Human Cancer ◽  
Adult Life ◽  
Fibroblast Growth Factors ◽  
Chromosomal Translocation ◽  
Fibroblast Growth ◽  
Lung Cancers ◽  
Mesenchymal Transition

FGFs (fibroblast growth factors) and their receptors (FGFRs) play essential roles in tightly regulating cell proliferation, survival, migration and differentiation during development and adult life. Deregulation of FGFR signalling, on the other hand, has been associated with many developmental syndromes, and with human cancer. In cancer, FGFRs have been found to become overactivated by several mechanisms, including gene amplification, chromosomal translocation and mutations. FGFR alterations are detected in a variety of human cancers, such as breast, bladder, prostate, endometrial and lung cancers, as well as haematological malignancies. Accumulating evidence indicates that FGFs and FGFRs may act in an oncogenic fashion to promote multiple steps of cancer progression by inducing mitogenic and survival signals, as well as promoting epithelial–mesenchymal transition, invasion and tumour angiogenesis. Therapeutic strategies targeting FGFs and FGFRs in human cancer are therefore currently being explored. In the present review we will give an overview of FGF signalling, the main FGFR alterations found in human cancer to date, how they may contribute to specific cancer types and strategies for therapeutic intervention.

Role of phytochemicals in the inhibition of epithelial–mesenchymal transition in cancer metastasis

2016 ◽  
Vol 7 (9) ◽  
pp. 3677-3685 ◽  
Author(s):  
Eun-Kyung Kim ◽  
Eun-Ju Choi ◽  
Trishna Debnath
Keyword(s):  
Growth Factors ◽  
Signaling Pathways ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Fibroblast Growth Factors ◽  
Fibroblast Growth ◽  
Scatter Factor ◽  
Mesenchymal Transition ◽  
Hepatocyte Growth

Epithelial–mesenchymal transition (EMT) development is controlled by several signaling pathways including Hedgehog, Wnt, fibroblast growth factors (FGF), hepatocyte growth factor/scatter factor (HGF),etc. Phytochemicals is very promising therapeutic candidate that inhibit the progression of EMT by inhibiting the signaling pathways.

scholarly journals EMT reversal in human cancer cells after IR knockdown in hyperinsulinemic mice

2016 ◽  
Vol 23 (9) ◽  
pp. 747-758 ◽  
Author(s):  
Zara Zelenko ◽  
Emily Jane Gallagher ◽  
Irini Markella Antoniou ◽  
Deepali Sachdev ◽  
Anupma Nayak ◽  
...  
Keyword(s):  
Insulin Receptor ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Human Cancer ◽  
Mortality Data ◽  
Primary Tumors ◽  
Mesenchymal Transition ◽  
Insulin Resistant ◽  
Human Cancer Cells

Type 2 diabetes (T2D) is associated with increased cancer risk and cancer-related mortality. Data herein show that we generated an immunodeficient hyperinsulinemic mouse by crossing theRag1−/−mice, which have no mature B or T lymphocytes, with the MKR mouse model of T2D to generate theRag1−/−(Rag/WT) andRag1−/−/MKR+/+(Rag/MKR) mice. The female Rag/MKR mice are insulin resistant and have significantly higher nonfasting plasma insulin levels compared with the Rag/WT controls. Therefore, we used these Rag/MKR mice to investigate the role of endogenous hyperinsulinemia on human cancer progression. In this study, we show that hyperinsulinemia in the Rag/MKR mice increases the expression of mesenchymal transcription factors,TWIST1andZEB1, and increases the expression of the angiogenesis marker, vascular endothelial growth factor A (VEGFA). We also show that silencing the insulin receptor (IR) in the human LCC6 cancer cells leads to decreased tumor growth and metastases, suppression of mesenchymal markers vimentin, SLUG, TWIST1 and ZEB1, suppression of angiogenesis markers,VEGFAandVEGFD, and re-expression of the epithelial marker, E-cadherin. The data in this paper demonstrate that IR knockdown in primary tumors partially reverses the growth-promoting effects of hyperinsulinemia as well as highlighting the importance of the insulin receptor signaling pathway in cancer progression, and more specifically in epithelial–mesenchymal transition.

scholarly journals Role of fibroblast growth factors in pancreatic cancer

2016 ◽  
Vol 62 (6) ◽  
pp. 622-629 ◽  
Author(s):  
D.A. Gnatenko ◽  
E.P. Kopantsev ◽  
E.D. Sverdlov
Keyword(s):  
Pancreatic Cancer ◽  
Growth Factors ◽  
Signaling Pathway ◽  
Cancer Progression ◽  
Fibroblast Growth Factors ◽  
Specific Marker ◽  
Fibroblast Growth ◽  
Complex Process ◽  
Wide Range ◽  
Fgfr Signaling

Fibroblast growth factors belong to a family of growth factors that are involved in various processes in organism and have a wide range of biological functions. Specifically for pancreas, FGFs are important during both organogenesis and carcinogenesis. One of the main characteristic of pancreatic cancer, is it close interaction between cancer and stromal cells via different factors, including FGF. Pathological changes in FGF/FGFR signaling pathway is a complex process. The remodeling effects and stimulation of tumor growth are mostly depend not only on types of receptors, but also from their isoforms. FGF/FGFR signaling pathway is a perspective specific marker for cancer progression, and a potential drug target, which can be used for treatment of pancreatic cancer.

scholarly journals The Cancer Microbiota: EMT and Inflammation as Shared Molecular Mechanisms Associated with Plasticity and Progression

2019 ◽  
Vol 2019 ◽  
pp. 1-16 ◽  
Author(s):  
Daniele Vergara ◽  
Pasquale Simeone ◽  
Marina Damato ◽  
Michele Maffia ◽  
Paola Lanuti ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Common Ground ◽  
Epithelial Mesenchymal Transition ◽  
Human Cancer ◽  
Malignant Progression ◽  
Pathogenic Microorganisms ◽  
Mesenchymal Transition ◽  
Host Interactions

With the advent of novel molecular platforms for high-throughput/next-generation sequencing, the communities of commensal and pathogenic microorganisms that inhabit the human body have been defined in depth. In the last decade, the role of microbiota-host interactions in driving human cancer plasticity and malignant progression has been well documented. Germ-free preclinical models provided an invaluable tool to demonstrate that the human microbiota can confer susceptibility to various types of cancer and can also modulate the host response to therapeutic treatments. Of interest, besides the detrimental effects of dysbiosis on cancer etiopathogenesis, specific microorganisms have been shown to exert protective activities against cancer growth. This has strong clinical implications, as restoration of the physiologic microbiota is being rapidly implemented as a novel anticancer therapeutic strategy. Here, we reviewed past and recent literature depicting the role of microbiota-host interactions in modulating key molecular mechanisms that drive human cancer plasticity and lead to malignant progression. We analyzed microbiota-host interactions occurring in the gut as well as in other anatomic sites, such as oral and nasal cavities, lungs, breast, esophagus, stomach, reproductive tract, and skin. We revealed a common ground of biological alterations and pathways modulated by a dysbiotic microbiota and potentially involved in the control of cancer progression. The molecular mechanisms most frequently affected by the pathogenic microorganisms to induce malignant progression involve epithelial-mesenchymal transition- (EMT-) dependent barrier alterations and tumor-promoting inflammation. This evidence may pave the way to better stratify high-risk cancer patients based on unique microenvironmental/microbial signatures and to develop novel, personalized, biological therapies.

scholarly journals Multifunctional Roles of miR-34a in Cancer: A Review with the Emphasis on Head and Neck Squamous Cell Carcinoma and Thyroid Cancer with Clinical Implications

Diagnostics ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 563
Author(s):  
David Kalfert ◽  
Marie Ludvikova ◽  
Martin Pesta ◽  
Jaroslav Ludvik ◽  
Lucie Dostalova ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Head And Neck ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Current Knowledge ◽  
Human Cancer ◽  
Squamous Carcinoma ◽  
Transcriptional Level ◽  
Mesenchymal Transition

MiR-34a belongs to the class of small non-coding regulatory RNAs and functions as a tumor suppressor. Under physiological conditions, miR-34a has an inhibitory effect on all processes related to cell proliferation by targeting many proto-oncogenes and silencing them on the post-transcriptional level. However, deregulation of miR-34a was shown to play important roles in tumorigenesis and processes associated with cancer progression, such as tumor-associated epithelial-mesenchymal transition, invasion, and metastasis. Moreover, further understanding of miR-34a molecular mechanisms in cancer are indispensable for the development of effective diagnosis and treatments. In this review, we summarized the current knowledge on miR-34a functions in human disease with an emphasis on its regulation and dysregulation, its role in human cancer, specifically head and neck squamous carcinoma and thyroid cancer, and emerging role as a disease diagnostic and prognostic biomarker and the novel therapeutic target in oncology.

scholarly journals The epithelial-mesenchymal transition and the cytoskeleton in bioengineered systems

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Susan E. Leggett ◽  
Alex M. Hruska ◽  
Ming Guo ◽  
Ian Y. Wong
Keyword(s):  
Cancer Progression ◽  
New Technologies ◽  
Epithelial Mesenchymal Transition ◽  
Human Cancer ◽  
Vimentin Expression ◽  
Mesenchymal Transition ◽  
Functional Changes ◽  
Surrounding Matrix ◽  
Planar Surfaces

AbstractThe epithelial-mesenchymal transition (EMT) is intrinsically linked to alterations of the intracellular cytoskeleton and the extracellular matrix. After EMT, cells acquire an elongated morphology with front/back polarity, which can be attributed to actin-driven protrusion formation as well as the gain of vimentin expression. Consequently, cells can deform and remodel the surrounding matrix in order to facilitate local invasion. In this review, we highlight recent bioengineering approaches to elucidate EMT and functional changes in the cytoskeleton. First, we review transitions between multicellular clusters and dispersed individuals on planar surfaces, which often exhibit coordinated behaviors driven by leader cells and EMT. Second, we consider the functional role of vimentin, which can be probed at subcellular length scales and within confined spaces. Third, we discuss the role of topographical patterning and EMT via a contact guidance like mechanism. Finally, we address how multicellular clusters disorganize and disseminate in 3D matrix. These new technologies enable controlled physical microenvironments and higher-resolution spatiotemporal measurements of EMT at the single cell level. In closing, we consider future directions for the field and outstanding questions regarding EMT and the cytoskeleton for human cancer progression.

scholarly journals The role of fibroblast growth factors and their receptors in prostate cancer

2004 ◽  
Vol 11 (4) ◽  
pp. 709-724 ◽  
Author(s):  
B Kwabi-Addo ◽  
M Ozen ◽  
M Ittmann
Keyword(s):  
Prostate Cancer ◽  
Growth Factors ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Fibroblast Growth Factors ◽  
Fibroblast Growth ◽  
Fgf Signaling ◽  
Prostate Cancer Progression ◽  
Fgf Receptor

Prostate cancer is the most common malignancy in men in the USA and the second leading cause of cancer deaths. Fibroblast growth factors (FGFs), including FGF1 (acidic FGF), FGF2 (basic FGF), FGF6 and FGF8 are all expressed at increased levels in prostate cancer as paracrine and/or autocrine growth factors for the prostate cancer cells. In addition, increased mobilization of FGFs from the extracellular matrix in cancer tissues can increase the availability of FGFs to cancer cells. Prostate cancer epithelial cells express all four types of FGF receptors (FGFR-1 to -4) at variable frequencies. Expression of FGFR-1 and FGFR-4 is most closely linked to prostate cancer progression, while the role of FGFR-2 remains controversial. Activation of FGF receptors can activate multiple signal transduction pathways including the phospholipase Cγ, phosphatidyl inositol 3-kinase, mitogen-activated protein kinase and signal transducers and activators of transcription (STAT) pathways, all of which play a role in prostate cancer progression. Sprouty proteins can negatively regulate FGF signal transduction, potentially limiting the impact of FGF signaling in prostate cancer, but in a significant fraction of prostate cancers there is decreased expression of Sprouty1 mRNA and protein. The effects of increased FGF receptor signaling are wide ranging and involve both the cancer cells and surrounding stroma, including the vasculature. The net result of increased FGF signaling includes enhanced proliferation, resistance to cell death, increased motility and invasiveness, increased angiogenesis, enhanced metastasis, resistance to chemotherapy and radiation and androgen independence, all of which can enhance tumor progression and clinical aggressiveness. For this reason, the FGF signaling system it is an attractive therapeutic target, particularly since therapies targeting FGF receptors and/or FGF signaling can affect both the tumor cells directly and tumor angiogenesis. A number of approaches that could target FGF receptors and/or FGF receptor signaling in prostate cancer are currently being developed.

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