CSNK1D inhibition suppresses head and neck squamous cell carcinoma progression through SHH and PTCH1 pathway

TL;DR

This study shows that inhibiting CSNK1D can slow the growth of head and neck cancer by affecting a key signaling pathway.

Contribution

The study reveals CSNK1D as a new driver of HNSCC progression and a potential therapeutic target.

Findings

CSNK1D is upregulated in HNSCC and linked to poor patient survival.

CSNK1D regulates the SHH-PTCH1 complex to activate the hedgehog pathway.

Inhibiting CSNK1D with SB-203580 offers a new treatment approach for HNSCC.

Abstract

Casein kinase 1δ (CK1δ, encoded by casein kinase 1 delta) (CSNK1D) is a serine/threonine protein kinase closely associated with cancer development. However, the biological functions of CSNK1D in head and neck squamous cell carcinoma (HNSCC) remain unclear. This study identifies CSNK1D as a previously unrecognized yet crucial regulator in the progression of HNSCC. CSNK1D expression levels were upregulated in tumor tissues and the up-regulation was positively correlated with poor survival in patients with HNSCC. Moreover, CSNK1D selectively bound SHH and PTCH1, and regulated the stability of the CSNK1D-SHH-PTCH1 complex to control the GLI1-BCL2 axis, leading to the downstream activation of the hedgehog pathway. SB-203580 could target and inhibit CSNK1D, offering new perspectives for the clinical treatment of HNSCC. Overall, CSNK1D is underscored as a vital oncogenic driver and promising therapeutic target for HNSCC.

Schematic illustration showing the suggested mechanism by which CSNK1D functions as an oncogene for HNSCC apoptosis through the hedgehog pathway. CSNK1D contributes to stable SHH and PTCH1 complexes to promote the nucleus entry of GLI1 to regulate BCL2 transcription.

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