NSD1 supports cell growth and regulates autophagy in HPV-negative head and neck squamous cell carcinoma

Iuliia Topchu ¹, Igor Bychkov ^1,2, Demirkan Gursel ³

⁰Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Division of Hematology/Oncology, Northwestern University, Chicago, IL, 60611, USA.

Cell Death Discovery +

|

February 12, 2024

View abstract on PubMed

Summary

Head and neck squamous cell carcinoma (HNSCC) involves the NSD1 gene, which drives tumor growth by activating Akt/mTORC1 signaling and autophagy. Targeting NSD1 may offer new therapeutic strategies for HPV-negative HNSCC.

Area Of Science

Oncology
Molecular Biology
Cancer Research

Background

Head and neck squamous cell carcinoma (HNSCC) is a prevalent cancer with a persistent 5-year survival rate of approximately 66%.
Identifying drivers of HPV-negative HNSCC is crucial for developing targeted therapies and improving patient outcomes.
NSD1, a histone methyltransferase, is implicated in HNSCC, with inactivating mutations correlating with better prognoses.

Purpose Of The Study

To investigate the role of NSD1 in regulating cell growth, signaling pathways, and autophagy in HNSCC.
To determine if NSD1 functions as a potential therapeutic target in head and neck cancer.

Main Methods

Depletion of NSD1 in HNSCC cell lines and in vivo models.
Analysis of cell growth, Akt/mTORC1 signaling pathway activation, and autophagic gene expression.
Assessment of protein levels for p62, LC3B-II, and ULK1, and evaluation of autophagic flux.

Main Results

NSD1 depletion significantly reduced HNSCC cell growth both in vitro and in vivo.
NSD1 was found to promote Akt/mTORC1 signaling pathway activation.
NSD1 knockdown induced an autophagic gene program, altered protein levels (p62, LC3B-II, ULK1), and disrupted autophagic flux.

Conclusions

NSD1 positively regulates Akt/mTORC1 signaling and autophagy in HNSCC.
These findings highlight novel functions of NSD1 in head and neck cancer.
NSD1 represents a potential therapeutic target for HNSCC treatment.

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