AACR 2018: How Splicing Factors May Impact Breast Cancer Cell Mitosis
Posted: Wednesday, May 2, 2018
A Dutch research team has identified several splicing factors critical to breast cancer cell proliferation, according to a poster presented at the 2018 American Association of Cancer Research (AACR) Annual Meeting (Abstract 1527). Led by Prof. Bob van de Water, of Leiden University, The Netherlands, the scientists found these factors impact the process by “modulating the expression of chromatid cohesion factors, thereby mediating the successful metaphase alignment and ultimate mitosis.”
Acknowledging the importance of growing evidence that RNA splicing is critical in breast cancer progression, Prof. van de Water and colleagues set out to evaluate the effect of siRNA-mediated knockdown of 244 splicing factors on proliferation in two highly proliferative breast cancer cell lines: MDA-MB-231 and Hs578T.
They discovered that both cell lines had a distinct polylobed nuclear phenotype. Increased levels of phospho-Histone H3 and a lack of normal metaphase alignment suggested a defect in mitosis, which they then confirmed by finding the presence of decreased RNA expression of sister chromatid cohesion factors MAU2, ESPL1, and SMC1A, and “interestingly, increased CDCA5 RNA levels,” they reported.
Ultimately, Prof. van de Water and colleagues were able to cause the death of these cells by retaining CDCA5 intron 1 upon splicing factor knockdown, which resulted in decreased CDCA5 protein levels and inaccurate metaphase alignment.
