# PABPC3 drives ovarian cancer metastasis and drug sensitivity by downregulating CLDN1 expression

## TL;DR

This study identifies PABPC3 as a key driver of ovarian cancer metastasis and drug resistance, offering a potential new target for treatment.

## Contribution

The study reveals PABPC3's novel role in promoting ovarian cancer metastasis by downregulating CLDN1 expression.

## Key findings

- PABPC3 overexpression increases ovarian cancer cell migration and metastasis in vivo.
- PABPC3 promotes metastasis by downregulating CLDN1, a tight junction protein.
- High PABPC3 expression correlates with poor survival in ovarian cancer patients.

## Abstract

Ovarian cancer remains one of the most lethal malignancies affecting women, with its high mortality rate primarily attributed to the aggressive metastatic nature of the disease, leading to late-stage diagnoses. The challenges posed by tumor metastasis and treatment resistance significantly complicate disease management and substantially reduce survival rates. Thus, elucidating the mechanisms underlying ovarian cancer metastasis is crucial for developing targeted therapies and improving patient outcomes. In this study, through single-nucleus RNA sequencing and analysis of clinical samples, we identify PABPC3 as a key regulator of ovarian cancer metastasis and patient survival. Functional experiments reveal that PABPC3 knockdown markedly inhibits ovarian cancer cell proliferation and migration, whereas its overexpression exerts the opposite effects. Furthermore, in vivo models confirm that PABPC3 overexpression significantly enhances metastatic potential. Mechanistically, PABPC3 promotes tumor metastasis by modulating the expression of CLDN1, a critical component of tight junctions. PABPC3 knockdown leads to a significant upregulation of CLDN1, while simultaneous CLDN1 knockdown partially rescues the migration-inhibitory effects induced by PABPC3 depletion. Additionally, clinical analyses demonstrate that high PABPC3 expression correlates with shorter overall survival, even among patients receiving chemotherapy. Notably, increased PABPC3 protein levels in metastatic lesions are associated with reduced progression-free survival. In conclusion, this study underscores the pivotal role of PABPC3 in ovarian cancer metastasis and patient prognosis, highlighting it as a potential therapeutic target for improving clinical outcomes.