FGF/FGFR signaling in adrenocortical development and tumorigenesis: novel potential therapeutic targets in adrenocortical carcinoma

Abstract

FGF/FGFR signaling regulates embryogenesis, angiogenesis, tissue homeostasis and wound repair by modulating proliferation, differentiation, survival, migration and metabolism of target cells. Understandably, compelling evidence for deregulated FGF signaling in the development and progression of different types of tumors continue to emerge and FGFR inhibitors arise as potential targeted therapeutic agents, particularly in tumors harboring aberrant FGFR signaling. There is first evidence of a dual role of the FGF/FGFR system in both organogenesis and tumorigenesis, of which this review aims to provide an overview. FGF-1 and FGF-2 are expressed in the adrenal cortex and are the most powerful mitogens for adrenocortical cells. Physiologically, they are involved in development and maintenance of the adrenal gland and bind to a family of four tyrosine kinase receptors, among which FGFR1 and FGFR4 are the most strongly expressed in the adrenal cortex. The repeatedly proven overexpression of these two FGFRs also in adrenocortical cancer is thus likely a sign of their participation in proliferation and vascularization, though the exact downstream mechanisms are not yet elucidated. Thus, FGFRs potentially offer novel therapeutic targets also for adrenocortical carcinoma, a type of cancer resistant to conventional antimitotic agents.

Mesenchymal stem cell secretome-loaded fibrin glue improves the healing of intestinal anastomosis

“…However, compared with MSCs secretome therapy, this kind of mono-factor therapy has significant disadvantages. At first, this therapy is not regulated by endogenous negative feedback mechanisms and has the potential to cause tissue hyperproliferation and carcinogenesis (Vajanto et al, 2002;Li et al, 2017;Tamburello et al, 2022). Secondly, this therapy has limited efficacy because tissue repair is accomplished by the concerted action of multiple factors, whereas MSCs secretome therapy has the advantage of containing numerous bioactive factors (Rhatomy et al, 2020).…”

Caffeic acid phenethyl ester suppresses metastasis of breast cancer cells by inactivating FGFR1 via MD2

“…FGFRs play a variety of roles in normal physiological and developmental processes, such as embryonic organ development, tissue repair, angiogenesis, and metabolism [17,18]. Substantial evidence suggests that abnormal FGFR activation is involved in the pathogenesis of cancer [19][20][21]. FGFR2 is considered to be a susceptibility gene for breast cancer, FGFR4 is a driving factor for breast cancer, and FGFR1 overexpression is found in nearly 50% of breast cancer patients.…”

Fibroblast Growth Factor-2 (FGF-2) Expression in Pterygia Using Cell Spot Arrays

“…The FGF-2 gene (gene locus: 4q28.1 ) encodes for a protein that acts as an important regulator of cell differentiation, cell migration and angiogenesis in normal and abnormal epithelia [ 9 ]. Additionally, the wound healing process, nervous and limb system development and functional maturation, combined with specific autocrine and paracrine effects, are FGF-mediated specific activities [ 10 , 11 ]. The present study analyzed the levels of FGF-2 in pterygia and normal conjunctiva epithelial cells by implementing the cell spot array technique on cytological slides combined with a digital image analysis algorithm to objectively measure the corresponding protein levels.…”