Back to Search
Start Over
Targeting SKA3 suppresses the proliferation and chemoresistance of laryngeal squamous cell carcinoma via impairing PLK1–AKT axis-mediated glycolysis
- Source :
- Cell Death and Disease, Vol 11, Iss 10, Pp 1-19 (2020), Cell Death & Disease
- Publication Year :
- 2020
- Publisher :
- Springer Science and Business Media LLC, 2020.
-
Abstract
- Spindle and kinetochore-associated complex subunit 3 (SKA3) is a well-known regulator of chromosome separation and cell division, which plays an important role in cell proliferation. However, the mechanism of SKA3 regulating tumor proliferation via reprogramming metabolism is unknown. Here, SKA3 is identified as an oncogene in laryngeal squamous cell carcinoma (LSCC), and high levels of SKA3 are closely associated with malignant progression and poor prognosis. In vitro and in vivo experiments demonstrate that SKA3 promotes LSCC cell proliferation and chemoresistance through a novel role of reprogramming glycolytic metabolism. Further studies reveal the downstream mechanisms of SKA3, which can bind and stabilize polo-like kinase 1 (PLK1) protein via suppressing ubiquitin-mediated degradation. The accumulation of PLK1 activates AKT and thus upregulates glycolytic enzymes HK2, PFKFB3, and PDK1, resulting in enhancement of glycolysis. Furthermore, our data reveal that phosphorylation at Thr360 of SKA3 is critical for its binding to PLK1 and the increase in glycolysis. Collectively, the novel oncogenic signal axis “SKA3-PLK1-AKT” plays a critical role in the glycolysis of LSCC. SKA3 may serve as a prognostic biomarker and therapeutic target, providing a potential strategy for proliferation inhibition and chemosensitization in tumors, especially for LSCC patients with PLK1 inhibitor resistance.
- Subjects :
- Male
Cancer Research
Cell division
Immunology
Mice, Nude
Cell Cycle Proteins
Protein Serine-Threonine Kinases
PLK1
Article
Tumour biomarkers
Mice
Cellular and Molecular Neuroscience
Proto-Oncogene Proteins
Biomarkers, Tumor
Animals
Humans
Molecular Targeted Therapy
lcsh:QH573-671
Head and neck cancer
Laryngeal Neoplasms
Chromosome separation
Protein kinase B
Cell Proliferation
Mice, Knockout
Oncogene
Squamous Cell Carcinoma of Head and Neck
lcsh:Cytology
Kinase
Cell growth
Chemistry
Cell Biology
Cancer metabolism
Drug Resistance, Neoplasm
Cancer research
Heterografts
Phosphorylation
Glycolysis
Microtubule-Associated Proteins
Proto-Oncogene Proteins c-akt
Signal Transduction
Subjects
Details
- ISSN :
- 20414889
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- Cell Death & Disease
- Accession number :
- edsair.doi.dedup.....6f505bdc7f6f06518df50ac03a75a64b