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14-3-3ζ silencing retards tongue squamous cell carcinoma progression by inhibiting cell survival and migration
1Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Abstract:
Our study aimed to investigate the isoform-specific distribution of 14-3-3 in tongue squamous cell carcinoma (TSCC) and their association with cancer progression, and to further discuss their roles in cancer cell survival. In this study, 42 TSCC specimens and their matched normal para-carcinoma sections were collected. The immunohistochemistry analysis identified that 14-3-3σ and ζ isoforms presented significantly higher expression in cancerous tissues compared with the matched normal tongue tissue sections. 14-3-3ζ expression was associated with tumor T stage, lymph node metastasis and poor prognosis of TSCC. In vitro study revealed that 14-3-3ζ silencing alleviated the proliferation and migration of TSCC cells while promoted cancer cell apoptosis. 14-3-3ζ could bind to and inactivate FOXO3a transcription factor, in turn leading to the movement of the 14-3-3ζ-FOXO3a complex from nucleus to cytoplasm, which was inhibited after 14-3-3ζ silencing. Both 14-3-3ζ and FOXO3a silencing increased caspase 3 and 9 activation, while reduced inner mitochondrial membrane potential. Collectively, 14-3-3ζ may serve as a hallmark and prognostic marker of TSCC. 14-3-3ζ can bind to the FOXO3a transcription factor to promote the export of the complex to the cytoplasm, leading to enhanced proliferation and migration of tongue cancer cells.
Insights
14-3-3ζ is overexpressed in tongue squamous cell carcinoma (TSCC) and linked to poor prognosis. Targeting 14-3-3ζ inhibits cancer cell growth and migration by affecting the FOXO3a pathway.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- 14-3-3 proteins are crucial regulators of cellular processes.
- Their specific roles in tongue squamous cell carcinoma (TSCC) progression remain incompletely understood.
Purpose of the Study:
- To investigate the expression patterns of 14-3-3 isoforms in TSCC.
- To determine the association of 14-3-3ζ with clinical parameters and prognosis.
- To elucidate the molecular mechanisms underlying 14-3-3ζ's role in TSCC cell survival and progression.
Main Methods:
- Immunohistochemistry was performed on 42 TSCC specimens and matched normal tissues.
- In vitro studies involved silencing 14-3-3ζ in TSCC cells.
- Western blotting and assessment of apoptosis markers were conducted.
Main Results:
- 14-3-3σ and 14-3-3ζ isoforms showed significantly higher expression in TSCC tissues.
- 14-3-3ζ expression correlated with advanced tumor stage, lymph node metastasis, and poorer prognosis.
- Silencing 14-3-3ζ reduced TSCC cell proliferation and migration while increasing apoptosis.
- 14-3-3ζ was found to bind and inactivate FOXO3a, promoting its cytoplasmic translocation.
Conclusions:
- 14-3-3ζ is upregulated in TSCC and serves as a potential prognostic marker.
- 14-3-3ζ promotes TSCC progression by inactivating FOXO3a and facilitating cell proliferation and migration.
- Targeting 14-3-3ζ may offer a therapeutic strategy for TSCC.
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