The Role of Hedgehog Signaling Pathway in Head and Neck Squamous Cell Carcinoma

Abstract

Head and neck squamous cell carcinoma (HNSCC) is the sixth leading malignancy worldwide, with a poor prognosis and limited treatment options. Molecularly targeted therapies for HNSCC are still lacking. However, recent reports provide novel insights about many molecular alterations in HNSCC that may be useful in future therapies. Therefore, it is necessary to identify new biomarkers that may provide a better prediction of the disease and promising targets for personalized therapy. The poor response of HNSCC to therapy is attributed to a small population of tumor cells called cancer stem cells (CSCs). Growing evidence indicates that the Hedgehog (HH) signaling pathway plays a crucial role in the development and maintenance of head and neck tissues. The HH pathway is normally involved in embryogenesis, stem cell renewal, and tissue regeneration. However, abnormal activation of the HH pathway is also associated with carcinogenesis and CSC regulation. Overactivation of the HH pathway was observed in several tumors, including basal cell carcinoma, that are successfully treated with HH inhibitors. However, clinical studies about HH pathways in HNSCC are still rare. In this review, we summarize the current knowledge and recent advances regarding the HH pathway in HNSCC and discuss its possible implications for prognosis and future therapy.

Elucidating Hedgehog pathway's role in HNSCC progression: insights from a 6-gene signature

“…Hedgehog signaling is involved in the development of teeth, lips, palate and salivary glands in the head and neck, and the importance of Hedgehog signaling in the occurrence of HNSCC was first reported in 2011 28 , 29 : high expression of Sonic hedgehog relates significantly to poor OS in patients with head and neck cancer. Later, Gregory et al found that Hedgehog signaling induces radiation resistance and matrix-driven tumor re-proliferation in HNSCC 30 .…”

Hair follicle stem cells promote epidermal regeneration under expanded condition

“…However, GSK3β serves as an inhibitory factor that downregulates both pathways. In addition, SFRP1, a downstream gene of the SHH pathway, has a similar effect on the Shh and Wnt pathways ( Cierpikowski et al, 2023 ). However, the downstream GLI family of the signaling pathway can activate both of these pathways.…”

Recent Advances in the Targeting of Head and Neck Cancer Stem Cells

“…Excessive SHh signaling in HNSCC is typically brought on by mutations in PTCH1, SMO, GLI1, and GLI2 or increased SHh ligand expression. Angiogenesis, EMT, and tumor development are all aided by abnormal SHh signaling, which makes HNSCC more aggressive [21]. Previous research indicates that SHh is essential for the maintenance and function of cancer stem cells.…”