NOTCH4 regulates colorectal cancer proliferation, invasiveness, and determines clinical outcome of patients.

Notch signal has complex roles in human malignancies, which might be attributed to the diversity of Notch receptors. Here, we set out to identify the association of NOTCH4 with colorectal cancer (CRC). In the hospital-based study cohort, we investigated NOTCH4 mRNA levels in primary CRC, as well as its association with clinicopathologic characteristics. Besides, NOTCH4 cDNA and siRNA was transfected into colorectal cancer cell line to elucidate its impact on tumor cell proliferation and migration. Results revealed a statistically significant lower expression of NOTCH4 mRNA in tumor specimens compared with that in control. NOTCH4 level in CRC was found to be related to tumor differentiation, invasion, and node metastasis. Moreover, it was demonstrated that NOTCH4 mRNA level could be an independent prognostic factor for both disease-free and overall survival of CRC patients. Overexpression of NOTCH4 in CRC cell lines suppressed tumor cell proliferation, migration, and invasion, while induced apoptosis. In the opposite, the malignant behavior of CRC cells was enhanced by NOTCH4 knockdown. These results demonstrated for the first time that NOTCH4 expression was decreased in CRC, which could determine tumor proliferation, relapse, and prognosis.