PhD defence

RNA splicing reprogramming to combat triple-negative breast cancer

• N. Liu

Date

Thursday 8 October 2026

Time

10:00 - 11:00 hour

Address

Academy Building
Rapenburg 73
2311 GJ Leiden

Supervisor(s)

• Prof.dr. B. van de Water
• dr. S.E. Le Dévédec

Summary

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with limited targeted treatment options. In this thesis, I investigated whether RNA splicing, the process by which cells edit and process RNA before producing proteins, could represent a vulnerability in TNBC.

Using large-scale RNAi screens, RNA sequencing, protein analysis, live-cell imaging and mouse models, I identified several splicing factors that are important for TNBC cell growth, migration and metastasis. One factor, SRSF7, emerged as a key regulator of cancer cell migration and metastatic growth. Reducing SRSF7 altered the processing of many RNAs and impaired aggressive tumour behaviour. I also identified proteins that interact with SRSF7 and contribute to cancer cell growth and migration. In addition, I investigated whether RNA splicing could be targeted with drugs. Inhibition of CLK kinases, which regulate the activity of splicing factors, strongly disrupted RNA splicing and reduced the growth and migration of TNBC cells. It also changed the location and movement of SRSF7 inside the cell nucleus. Together, these findings show that RNA splicing is not simply a basic cellular process, but also contributes to the aggressive behaviour of TNBC. Targeting splicing regulation may therefore offer a new therapeutic strategy for this difficult-to-treat breast cancer. However, because RNA splicing is also essential in healthy cells, further research is needed to determine how such treatments can be used effectively and safely.

PhD dissertations

Approximately one week after the defence, PhD dissertations by Leiden PhD students are available digitally through the Leiden Repository, that offers free access to these PhD dissertations. Please note that in some cases a dissertation may be under embargo temporarily and access to its full-text version will only be granted later.

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