# SNW1 promotes lymphatic metastasis in bladder cancer by modulating SRPK1 splicing

## TL;DR

SNW1 promotes bladder cancer metastasis by altering SRPK1 splicing, offering a potential therapeutic target.

## Contribution

Identifies SNW1 as a novel mediator of bladder cancer metastasis through splicing modulation of SRPK1.

## Key findings

- Elevated SNW1 levels correlate with lymph node metastasis and poor outcomes in bladder cancer.
- SNW1 modulates SRPK1 splicing via interactions with NUDT21 and CPSF6.
- SRPK1 inhibition suppresses bladder cancer metastasis in preclinical models.

## Abstract

The overall survival of patients with metastatic bladder cancer (BCa) remains poor. There is a lack of effective therapies and reliable biomarkers for metastatic BCa. BCa cells initially disseminate via the pelvic lymph nodes (LN). This study identified that elevated levels of SNW1 have been correlated with LN metastasis and unfavorable patient outcomes. SNW1 enhances the migratory and invasive capabilities of BCa cells. Further investigation revealed that SNW1 modulates SRPK1 splicing, resulting in opposite expression changes in two distinct SRPK1 transcripts. The effect of SNW1 on promoting metastasis is dependent on SRPK1 protein expression. Mechanistic investigations revealed that SNW1 interacts with core spliceosome components NUDT21 and CPSF6 to modulate SRPK1 splicing. This study underscores the pivotal contribution of RNA splicing in BCa metastasis, with SNW1 serving as a key mediator. The identification of key regulatory molecules provides valuable insights into potential therapeutic targets for clinical intervention in metastatic BCa.

•SNW1 facilitates lymph node metastasis in bladder cancer through an SRPK1-dependent mechanism•SNW1 modulates the splicing of SRPK1 by interacting with NUDT21/CPSF6•Treatment with an SRPK1 inhibitor suppresses bladder cancer metastasis

SNW1 facilitates lymph node metastasis in bladder cancer through an SRPK1-dependent mechanism

SNW1 modulates the splicing of SRPK1 by interacting with NUDT21/CPSF6

Treatment with an SRPK1 inhibitor suppresses bladder cancer metastasis

Biochemistry; Cancer; Omics