The Suitability of FGF21 and FGF23 as New Biomarkers in Endometrial Cancer Patients

Cymbaluk‐Płoska, Aneta; Gargulińska, Paula; Chudecka‐Głaz, Anita; Kwiatkowski, Sebastian; Pius-Sadowska, Ewa

doi:10.3390/diagnostics10060414

Cited by 20 publications

(21 citation statements)

References 39 publications

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“…FGF21 and FGF23 expression have been implicated in endometrial cancer due to their association with increased expression of leptin (LEP), a hormone produced in adipose tissue. Serum FGF21 and LEP concentrations are increased in patients with endometrial cancer, and associated with low differentiation and higher grade of tumor [ 119 ]. Circulating FGF21 has also been associated with increased risk of CRC [ 118 ].…”

Section: Fgf Signaling Diversity In Cancermentioning

confidence: 99%

Fibroblast Growth Factor Receptors (FGFRs) and Noncanonical Partners in Cancer Signaling

Ferguson

Smith

Francavilla

2021

Cells

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Increasing evidence indicates that success of targeted therapies in the treatment of cancer is context-dependent and is influenced by a complex crosstalk between signaling pathways and between cell types in the tumor. The Fibroblast Growth Factor (FGF)/FGF receptor (FGFR) signaling axis highlights the importance of such context-dependent signaling in cancer. Aberrant FGFR signaling has been characterized in almost all cancer types, most commonly non-small cell lung cancer (NSCLC), breast cancer, glioblastoma, prostate cancer and gastrointestinal cancer. This occurs primarily through amplification and over-expression of FGFR1 and FGFR2 resulting in ligand-independent activation. Mutations and translocations of FGFR1-4 are also identified in cancer. Canonical FGF-FGFR signaling is tightly regulated by ligand-receptor combinations as well as direct interactions with the FGFR coreceptors heparan sulfate proteoglycans (HSPGs) and Klotho. Noncanonical FGFR signaling partners have been implicated in differential regulation of FGFR signaling. FGFR directly interacts with cell adhesion molecules (CAMs) and extracellular matrix (ECM) proteins, contributing to invasive and migratory properties of cancer cells, whereas interactions with other receptor tyrosine kinases (RTKs) regulate angiogenic, resistance to therapy, and metastatic potential of cancer cells. The diversity in FGFR signaling partners supports a role for FGFR signaling in cancer, independent of genetic aberration.

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Section: Fgf Signaling Diversity In Cancermentioning

confidence: 99%

Fibroblast Growth Factor Receptors (FGFRs) and Noncanonical Partners in Cancer Signaling

Ferguson

Smith

Francavilla

2021

Cells

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“…Higher RNA levels of both leptin and leptin receptors were found in prostate cancer patients than in healthy controls in a study including 176 men [ 30 ]. Leptin levels in patients with endometrial cancer were significantly higher than those in the control group [ 31 ].…”

Section: Leptin and Leptin Receptor Expression In Cancermentioning

confidence: 99%

Leptin and Cancer: Updated Functional Roles in Carcinogenesis, Therapeutic Niches, and Developments

Lin

Hsiao

2021

IJMS

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Leptin is an obesity-associated adipokine that is known to regulate energy metabolism and reproduction and to control appetite via the leptin receptor. Recent work has identified specific cell types other than adipocytes that harbor leptin and leptin receptor expression, particularly in cancers and tumor microenvironments, and characterized the role of this signaling axis in cancer progression. Furthermore, the prognostic significance of leptin in various types of cancer and the ability to noninvasively detect leptin levels in serum samples have attracted attention for potential clinical applications. Emerging findings have demonstrated the direct and indirect biological effects of leptin in regulating cancer proliferation, metastasis, angiogenesis and chemoresistance, warranting the exploration of the underlying molecular mechanisms to develop a novel therapeutic strategy. In this review article, we summarize and integrate transcriptome and clinical data from cancer patients together with the recent findings related to the leptin signaling axis in the aforementioned malignant phenotypes. In addition, a comprehensive analysis of leptin and leptin receptor distribution in a pancancer panel and in individual cell types of specific organs at the single-cell level is presented, identifying those sites that are prone to leptin-mediated tumorigenesis. Our results shed light on the role of leptin in cancer and provide guidance and potential directions for further research for scientists in this field.

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“…In endometrial cancer, no change in the FGF23 plasma concentration is observed ( Cymbaluk-Płoska et al, 2020 ), whereas the FGF23 plasma concentration goes up in advanced-stage epithelial ovarian cancer (EOC) ( Tebben et al, 2005 ), and a defined FGF23 SNP is associated with better prognosis in this tumor entity ( Meng et al, 2014 ). Breast cancer may be associated with oncogenic osteomalacia and raised FGF23 levels ( Savva et al, 2019 ).…”

Section: Fgf23 and Cancermentioning

confidence: 99%

Role of Fibroblast Growth Factor 23 (FGF23) and αKlotho in Cancer

Ewendt

Feger

Föller

2021

Front. Cell Dev. Biol.

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Together with fibroblast growth factors (FGFs) 19 and 21, FGF23 is an endocrine member of the family of FGFs. Mainly secreted by bone cells, FGF23 acts as a hormone on the kidney, stimulating phosphate excretion and suppressing formation of 1,25(OH)2D3, active vitamin D. These effects are dependent on transmembrane protein αKlotho, which enhances the binding affinity of FGF23 for FGF receptors (FGFR). Locally produced FGF23 in other tissues including liver or heart exerts further paracrine effects without involvement of αKlotho. Soluble Klotho (sKL) is an endocrine factor that is cleaved off of transmembrane Klotho or generated by alternative splicing and regulates membrane channels, transporters, and intracellular signaling including insulin growth factor 1 (IGF-1) and Wnt pathways, signaling cascades highly relevant for tumor progression. In mice, lack of FGF23 or αKlotho results in derangement of phosphate metabolism and a syndrome of rapid aging with abnormalities affecting most organs and a very short life span. Conversely, overexpression of anti-aging factor αKlotho results in a profound elongation of life span. Accumulating evidence suggests a major role of αKlotho as a tumor suppressor, at least in part by inhibiting IGF-1 and Wnt/β-catenin signaling. Hence, in many malignancies, higher αKlotho expression or activity is associated with a more favorable outcome. Moreover, also FGF23 and phosphate have been revealed to be factors relevant in cancer. FGF23 is particularly significant for those forms of cancer primarily affecting bone (e.g., multiple myeloma) or characterized by bone metastasis. This review summarizes the current knowledge of the significance of FGF23 and αKlotho for tumor cell signaling, biology, and clinically relevant parameters in different forms of cancer.

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The Suitability of FGF21 and FGF23 as New Biomarkers in Endometrial Cancer Patients

Cited by 20 publications

References 39 publications

Fibroblast Growth Factor Receptors (FGFRs) and Noncanonical Partners in Cancer Signaling

Fibroblast Growth Factor Receptors (FGFRs) and Noncanonical Partners in Cancer Signaling

Leptin and Cancer: Updated Functional Roles in Carcinogenesis, Therapeutic Niches, and Developments

Role of Fibroblast Growth Factor 23 (FGF23) and αKlotho in Cancer

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