EGFR targeting agents are clinically effective in treating KRAS and BRAF wild-type tumors, although no clinical benefit may be proven for KRAS or BRAF mutant tumors. Thus, drug induced overexpression of ATF3 might have beneficial effects in just a subset of colon cancer cells. This important result will be further addressed in future experiments, where lack of ATF3 overexpression well as ATF3 function will be examined in colon cancer cells with different genetic background. In line with our findings in HCT116 colon cancer, growth suppressive qualities of ATF3 were proposed in a report by Oh et al., describing that ATF3 functions as tumorinhibiting element in HeLa cervical cancer cells in vitro. Furthermore, Lu and co workers elegantly Metastatic carcinoma demonstrated that ATF3 is capable of controlling a Rasmediated tumorigenicity of murine fibroblasts in in vivo model, as well as in an in vitro, thus supporting our hypothesis of a tumor suppressive part. To conclude, these errors reflect the complex role of ATF3 which might not entirely depend on the investigated cell line. The natural purpose of ATF3 in vivo may possibly rather highly rely on the microenvironment of the defined cyst entity. One clinical significance of our studies is the fact that therapy caused up regulation of ATF3, as for example via inhibition or COX 2 inhibition, might be valuable in certain tumors for reducing growth and metastasis. With respect to COX 2 inhibitors, experimental studies have nicely shown that ATF3 may mediate anti neoplastic and anti invasive ramifications of such non-steroidal anti inflammatory drugs. In this review, overexpression of ATF3 inhibited invasion into a similar degree as sulindac sulfide treatment and antisense ATF3 improved invasion in vitro. Where transfection of cancer (-)-MK 801 cells having a full-length ATF3 vector suppressed tumorigenicity and invasiveness in vitro and tumor growth in vivo, that tumor suppressive effect of ATF3 can be supported by their findings. Nevertheless, this group wasn’t in a position to validate within an in vivo environment that lack of ATF3 function is alternatively related to improved growth rates and metastasis, thus our research further increases the information on function beyond these features. We observed an enhanced migration behavior after inhibition in vitro and hypothesized that loss in ATF3 function might also lead to an increased cyst metastasis in vivo, an element that has not been adequately examined to date. In subsequent hepatic and peritoneal tumor models, we could show a substantial escalation in tumor burden, cancer distribution, and tumorigenicity upon more down managing ATF3. Therefore, we suggest that ATF3 functions as a tumefaction suppressor and anti metastatic aspect in HCT116 cancer of the colon.