Most colon cancers have a chromosomal instability and show an abnormal number of chromosomes in the nucleus. This hallmark enables the tumor cells of having an increased mutation rate and therefore enhanced aggressiveness in more advanced stages. Our previous data showed that high expression of DIAPH2 in colon cancer correlates with low tumor stage, grading and nodal stage. Moreover, high DIAPH2 expression was associated with improved overall survival in patients. There are hints that DIAPH2 is crucial for intact chromosomal arrangement during the metaphase of cell division and thus possibly regulates chromosomal stability.

The goal of this project is to elucidate whether DIAPH2 is a tumor suppressor in colon cancer cells, and to reveal the underlying mechanism. For this purpose, we plan to perform mechanistic investigations and clinical studies from patient’s samples: First, we plan to reduce or increase the DIAPH2 expression in colon cancer cells with the help of retroviral vectors, in order to examine the effects of these manipulations on chromosomal stability. Thereafter, we will examine the effects of a DIAPH2 overexpression in a chromosomally instable colon cancer cell line with a low DIAPH2 expression, on tumor growth and metastasis in a mouse model. Subsequently, with the help of colon cancer and liver metastasis samples from patients, we will investigate how the DIAPH2 expression differentiates between benign preliminary stages of colon cancer, cancer and distant metastasis. Depending on the results, mutation analysis of DIAPH2 in differently advanced colon cancers are planned to be performed.