USP20 competitively binds to STUB1 to enhance CTSL expression and promote epithelial‐mesenchymal transition in head and neck squamous cell carcinoma
Lunhua Guo, Baihui Zhang, Xiaoqiao Cui, Xueying Wang, Jiaqing Xiao, Susheng Miao, Kaibin Song, Ji Sun
TL;DR
This study shows how USP20 helps a protein called CTSL become more stable, which makes head and neck cancer more aggressive and resistant to treatment.
Contribution
The study identifies USP20 as a new regulator of CTSL through competitive binding with STUB1, offering a potential target for treating metastatic HNSCC.
Findings
USP20 deubiquitinates and stabilizes CTSL, promoting cancer progression.
USP20 competes with STUB1 for CTSL binding, enhancing tumor malignancy.
Targeting USP20 increases cancer cell sensitivity to chemotherapy drugs like cisplatin and paclitaxel.
Abstract
Metastatic head and neck squamous cell carcinoma (mHNSCC) poses a significant threat to patient survival. Previous studies have identified cathepsin L (CTSL) as a key driver of tumourigenesis, metastasis and chemoresistance. However, the regulatory mechanisms underlying CTSL expression remain poorly understood. A specific deubiquitinase responsible for CTSL expression was identified through treatment with broad‐spectrum deubiquitinase inhibitors and mass spectrometry analysis. The colocalization of CTSL and USP20 in the cytoplasm was examined using confocal microscopy. The effects of CTSL or USP20 depletion on tumour biological behaviour were evaluated through various in vitro and in vivo assays. We identified USP20 as a specific deubiquitinase of CTSL. USP20 mediates the deubiquitination and stabilization of CTSL, thereby promoting epithelial‐to‐mesenchymal transition and cancer stem…
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Taxonomy
TopicsUbiquitin and proteasome pathways · Hedgehog Signaling Pathway Studies · TGF-β signaling in diseases