Characterizing C3orf52 and TSC1 as Emerging Molecular Targets in Triple-Negative and Multifocal Breast Cancer 2258409

Abstract Introduction Triple-negative and multifocal breast cancers lack effective targeted therapies and remain associated with poor clinical outcomes. Bioinformatic analysis identified two underexplored genes, C3orf52 and TSC1, that may influence tumor progression. C3orf52 is upregulated in multifocal breast cancer and appears within a prognostic seven-gene signature, while TSC1, a regulator of the mTOR pathway, is modestly expressed in select cancer cell lines. This project investigates how these genes contribute to cancer growth and whether they represent viable therapeutic targets. Methods Gene-expression datasets were analyzed to compare C3orf52 and TSC1 levels across breast, kidney, and prostate cancer samples. Functional studies are being performed using CRISPR-Cas9 knockout and quantitative RT-PCR assays to evaluate changes in proliferation and invasion in established cell lines. The mTOR inhibitor temsirolimus is used to assess pathway dependence in TSC1-expressing cells. Results Bioinformatic analysis confirmed upregulation of C3orf52 in multifocal breast cancer and elevated expression across several tumor types. Knockout experiments are in progress to determine its effect on proliferation. TSC1 expression correlated with mTOR pathway activation, and preliminary inhibitor studies demonstrated reduced viability in HCC1937 and A498 cells, supporting its relevance as a therapeutic target. Conclusion C3orf52 and TSC1 represent potential molecular regulators of tumor progression in aggressive cancers. Ongoing functional validation will clarify whether these genes cooperate in promoting proliferation and whether targeting the mTOR pathway or C3orf52 expression can inform development of new therapeutic strategies for breast and related cancers. Funding Source n/a Topic Categories Tumor Immunology: Checkpoints, Prevention, and Treatment (TIPT)