# The roles of CD24-Sec14 like lipid binding 2 (SEC14L2) axis in the neoplastic progression of oral squamous cell carcinomas

## TL;DR

This study explores how CD24 and SEC14L2 contribute to oral cancer progression and immune response, suggesting CD24 as a potential treatment target.

## Contribution

The study identifies the CD24-SEC14L2 axis as a novel driver of oncogenicity and immune modulation in oral squamous cell carcinoma.

## Key findings

- CD24 expression increases migration, invasion, and SEC14L2 levels in oral cancer cells.
- CD24 suppression with doxycycline significantly reduces tumor growth in mouse models.
- SEC14L2 is upregulated in HNSCC/OSCC and linked to poor survival outcomes.

## Abstract

Immune stimulation or escape are critical factors determining the survival of malignancies, including oral squamous cell carcinoma (OSCC) and head and neck SCC (HNSCC). CD24 (CD24A in mice) is a glycoprotein anchored to cell membranes, modulating macrophages' immune responses, cell interaction, tumorigenesis, and stemness. However, its roles in the OSCC pathogenesis are still controversial. The modulation of CD24 on the oncogenicity and immunity of OSCC were investigated in this study.

Knockdown approaches and the establishment of stable tet-off CD24 expression cell subclones were used in cell and mouse models for phenotypic and transcriptomic analysis. Bioinformatic assessments were performed to specify the clinicopathological implications.

CD24 expression modulated the increase of migration and invasion and the upregulation of phosphatidylcholine/phosphatidylinositol transfer protein Sec14 like lipid binding 2 (SEC14L2) expression. The syngeneic grafts of CD24 tet-off expressing murine OSCC cell subclones exhibited modest changes of immune cell infiltration within tumors and were devoid of immune profile disruption in the recipient's neck lymph node and spleen. The shutdown of CD24 with doxycycline treatment drastically suppressed the growth of CD24 tet-off tumors. A correlation between CD24 expression and myeloid dendritic cell population was noted in murine and human OSCC tissue. Concordances in CD24 and SEC14L2 expression and oncogenic induction were noted in murine tumors. SEC14L2 was upregulated in HNSCC/OSCC tumors, and it was an unfavorable survival predictor.

This study's elucidation of the oncogenic potential of the CD24-SEC14L2 axis may signify the therapeutic efficacy of CD24 targeting for HNSCC/OSCC.