SKA1 promotes oncogenic properties in oral dysplasia and oral squamous cell carcinoma, and augments resistance to radiotherapy

TL;DR

The gene SKA1 promotes cancer growth and resistance to radiation in oral cancer and may serve as a marker for poor outcomes.

Contribution

SKA1's role in promoting radioresistance in oral squamous cell carcinoma is newly identified.

Findings

SKA1 enhances proliferation, migration, and radioresistance in oral cancer cell lines.

High SKA1 expression correlates with reduced survival in radiotherapy-treated oral cancer patients.

SKA1 activates distinct oncogenic pathways in oral dysplasia compared to advanced cancer.

Abstract

Oral squamous cell carcinoma (OSCC) is a malignancy associated with high morbidity and mortality, yet treatment options are limited. In addition to genetic alterations, aberrant gene expression contributes to the pathology of malignant diseases. In the present study, we identified 629 genes consistently dysregulated between OSCC and normal oral mucosa across nine public gene expression datasets. Among them, mitosis‐related genes were significantly enriched, including spindle and kinetochore‐associated complex subunit 1 (SKA1), whose roles in OSCC had been studied only to a very limited extent. We show that SKA1 promoted proliferation and colony formation in 2D and 3D, shortened the duration of metaphase, and increased the migration of OSCC cell lines. In addition, high SKA1 expression enhanced radioresistance, a previously unknown effect of this gene, which was accompanied by a reduction of radiation‐induced senescence. SKA1 was also upregulated in a subset of advanced oral premalignancies and promoted tumor‐relevant properties in a corresponding cell line. Gene expression patterns evoked by SKA1 overexpression confirmed that this gene is able to advance properties required for both early and advanced stages of tumorigenesis. In summary, our data show that SKA1 contributes to malignant progression in OSCC and may be a useful marker of radioresistance in this disease.

The mitosis‐related gene SKA1 was among 629 genes consistently dysregulated in OSCC across nine public gene expression datasets. In OSCC cell lines, SKA1 promoted proliferation and migration, enhanced radioresistance, and reduced radiation‐induced senescence. Accordingly, SKA1 expression correlated negatively with survival in radiotherapy‐treated OSCC patients. SKA1 promoted tumor‐related properties also in oral dysplasia, but activated different oncogenic pathways than in OSCC.

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