Diaphanous-related formin 1 as a target for tumor therapy.

Formins nucleate actin and stabilize microtubules (MTs). Expression of the formin Diaphanous homolog 1 (DIAPH1) is increased in malignant colon carcinoma cells, while expression of DIAPH3 is up-regulated in breast and prostate carcinoma cells. Both DIAPH1 isoforms are required to stabilize interphase MTs of cancer cells, and it has been shown that loss of this function decreases the metastatic potential of these cells. Moreover, depletion of DIAPH3 increases the sensitivity of breast and prostate carcinoma cells to taxanes. In contrast with DIAPH1 + 3, DIAPH2 regulates metaphase MTs of tumor cells by stabilizing binding of kinetochore MTs to chromosomes. Depletion of DIAPH2 impairs chromosome alignment, thus proper chromosome segregation during mitosis. In summary, expression of DIAPH formins in tumor cells is essential for stabilizing interphase or metaphase MTs, respectively. Thus, it would be very interesting to analyze if tumor cells exhibiting low DIAPH expression are more sensitive to taxanes than those with high DIAPH expression.