FGF signalling facilitates cervical cancer progression

Abstract

Cervical cancer is one of the most frequently diagnosed cancers in women worldwide. While cervical cancer is caused by human papillomavirus (HPV), not all females infected with HPV develop the disease, suggesting that other factors might facilitate its progression. Growing evidence supports the involvement of the fibroblast growth factor receptor (FGFR) axis in several cancers, including gynecological. However, for cervical cancer, the molecular mechanisms that underpin the disease remain poorly understood, including the role of FGFR signaling. The aim of this study was to investigate FGF(R) signaling in cervical cancer through bioinformatic analysis of cell line and patient data and through detailed expression profiling, manipulation of the FGFR axis, and downstream phenotypic analysis in cell lines (HeLa, SiHa, and CaSki). Expression (protein and mRNA) analysis demonstrated that FGFR1b/c, FGFR2b/c, FGFR4, FGF2, FGF4, and FGF7 were expressed in all three lines. Interestingly, FGFR1 and 2 localized to the nucleus, supporting that nuclear FGFRs could act as transcription factors. Importantly, 2D and 3D cell cultures demonstrated that FGFR activation can facilitate cell functions correlated with invasive disease. Collectively, this study supports an association between FGFR signaling and cervical cancer progression, laying the foundations for the development of therapeutic approaches targeting FGFR in this disease.

FGF–FGFR signaling promotes the development of invasive cervical cancer

“…This work presented by Mahmood et al in The FEBS Journal [7] clearly indicated a crucial role for FGFR signaling in malignancy development during the progression of cervical cancer. The obtained data suggest, as in the case of other tumors, that small‐molecule FGFR inhibitors might be successfully used in targeted therapy against cervical cancer and improve patient outcomes.…”

GPR30-mediated non-classic estrogen pathway in mast cells participates in endometriosis pain via the production of FGF2

“…FGFR1 inhibitors are used in the treatment of various diseases. Zhang et al reported that the FGFR1 inhibitor PD173074 effectively inhibited p-FGFR1 phosphorylation and increased the threshold for mechanical pain in rats with myofascial pain syndrome (65). NSC12 is a small molecule inhibitor that could orally inhibit the interaction of FGF2/FGFR.…”

Role of developmental pathways in disease

“…Also featured in this Subject Collection is a research article from Hiba‐Tun‐Noor Afshan Mahmood et al . [6] that investigates the role of fibroblast growth factor receptor (FGFR) signaling in cervical cancer. Fibroblast growth factor receptor regulates numerous biological processes during normal development and is hyperactivated in many cancers.…”