USP30 promotes the progression of breast cancer by stabilising Snail

Breast cancer (BC) is the most prevalent tumour in women worldwide. USP30 is a deubiquitinase that has been previously reported to promote tumour progression and lipid synthesis in hepatocellular carcinoma. However, the role of USP30 in breast cancer remains unclear. Therefore, we investigated its b...

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Bibliographic Details
Published in:Cancer gene therapy 2024-03, Vol.31 (3), p.472-483
Main Authors: Sun, Kai, Liao, Shichong, Yao, Xinrui, Yao, Feng
Format: Article
Language:English
Subjects:
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Biomedical and Life Sciences
Biomedicine
Breast cancer
Breast Neoplasms - pathology
Carcinoma, Hepatocellular
Cell Line, Tumor
Cell migration
Cell Movement - genetics
Cell Proliferation
Drug resistance
Female
Gene Expression
Gene Expression Regulation, Neoplastic
Gene Therapy
Hepatocellular carcinoma
Humans
Liver Neoplasms - genetics
Medical prognosis
Metastasis
Paclitaxel
Paclitaxel - pharmacology
Targeted cancer therapy
Therapeutic targets
Tumors
Womens health
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Summary:Breast cancer (BC) is the most prevalent tumour in women worldwide. USP30 is a deubiquitinase that has been previously reported to promote tumour progression and lipid synthesis in hepatocellular carcinoma. However, the role of USP30 in breast cancer remains unclear. Therefore, we investigated its biological action and corresponding mechanisms in vitro and in vivo. In our study, we found that USP30 was highly expressed in breast cancer samples and correlated with a poor patient prognosis. Knockdown of USP30 significantly suppressed the proliferation, invasion and migration abilities of BC cells in vitro and tumour growth in vivo, whereas overexpression of USP30 exhibited the opposite effect. Mechanistically, we verified that USP30 interacts with and stabilises Snail to promote its protein expression through deubiquitination by K48-linked polyubiquitin chains and then accelerates the EMT program. More importantly, USP30 reduced the chemosensitivity of BC cells to paclitaxel (PTX). Collectively, these data demonstrate that USP30 promotes the BC cell EMT program by stabilising Snail and attenuating chemosensitivity to PTX and may be a potential therapeutic target in BC.
ISSN:0929-1903
1476-5500
DOI:10.1038/s41417-023-00718-8