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Alternatively spliced ANLN isoforms synergistically contribute to the progression of head and neck squamous cell carcinoma
- Source :
- Cell Death and Disease, Vol 12, Iss 8, Pp 1-14 (2021), Cell Death & Disease
- Publication Year :
- 2021
- Publisher :
- Nature Publishing Group, 2021.
-
Abstract
- Head and neck squamous cell carcinoma (HNSCC) is a common cancer with high mortality. Anilin actin-binding protein (ANLN) has been reported to be associated with carcinogenesis in multiple tumors. However, the expression pattern and functional effects of ANLN in HNSCC remain to be unclear. Clinical data and online databases were used to analyze the expression of ANLN and its relationship with HNSCC patient survival. Expression of two major splice variants of ANLN was assessed in HNSCC tissues and cell lines. The functional effects and related mechanisms of ANLN isoforms were investigated in HNSCC in vitro and in vivo. Our study showed that patients with high expression of ANLN had a poor prognosis. The two primary isoforms of ANLN transcripts ANLN-201 and ANLN-210 were highly expressed in HNSCC tissues and cell lines. Knockout of ANLN restrained cell proliferation, migration, and invasion of SCC-9 cells. Mechanically, ANLN-201 could interact with c-Myc to keep its protein stability, thereby playing a oncogenic role in HNSCC. ANLN-210 could be transferred to macrophages via exosomes by binding to RNA-binding protein hnRNPC. Exosomal ANLN-210 promoted macrophage polarization via PTEN/PI3K/Akt signaling pathway, thus stimulating tumor growth of HNSCC. ANLN was an independent prognostic factor in patients with HNSCC. Alternatively spliced ANLN isoforms collaboratively promote HNSCC tumorigenesis in vitro and in vivo, which might provide the in-depth role and mechanism of ANLN in HNSCC development.
- Subjects :
- Cancer Research
Exosomes
medicine.disease_cause
Metastasis
ANLN
Cell Movement
Protein Isoforms
Head and neck cancer
Protein Stability
Microfilament Proteins
Cell Polarity
Prognosis
Cancer metabolism
Gene Expression Regulation, Neoplastic
Head and Neck Neoplasms
Disease Progression
Protein Binding
Cancer microenvironment
HNRNPC
Immunology
Biology
Article
Proto-Oncogene Proteins c-myc
Cellular and Molecular Neuroscience
stomatognathic system
Cell Line, Tumor
medicine
otorhinolaryngologic diseases
Humans
PTEN
Neoplasm Invasiveness
RNA, Messenger
neoplasms
PI3K/AKT/mTOR pathway
Proportional Hazards Models
Base Sequence
QH573-671
Squamous Cell Carcinoma of Head and Neck
Akt/PKB signaling pathway
Cell growth
Heterogeneous-Nuclear Ribonucleoprotein Group C
Macrophages
Cell Biology
medicine.disease
Head and neck squamous-cell carcinoma
Alternative Splicing
stomatognathic diseases
Cancer research
biology.protein
Carcinogenesis
Cytology
Subjects
Details
- Language :
- English
- ISSN :
- 20414889
- Volume :
- 12
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- Cell Death and Disease
- Accession number :
- edsair.doi.dedup.....23d9a1f5a7fa463173468f168b4853e3