Fibulin-5 contributes to colorectal cancer cell apoptosis via the ROS/MAPK and Akt signal pathways by downregulating transient receptor potential cation channel subfamily V member 1.

Fibulin-5, a multifunctional extracellular matrix (ECM) protein, is secreted into the ECM, regulating metastasis and invasion in many malignant tumors. However, its role in colorectal cancer (CRC) has not been reported. In this study, we detected the expression of fibulin-5 in 56 CRC patients and eight CRC cell lines, revealing that fibulin-5 was expressed lower in CRC tumor tissues than in peritumor tissues. Furthermore, our study verified that fibulin-5 promoted cell apoptosis and reactive oxygen species (ROS) production by inhibiting transient receptor potential cation channel subfamily V member 1 (TRPV1) in CRC cells. Moreover, NAC (the scavenger of ROS), SB203580 (the inhibitor of p38), PD98059 (the inhibitor of ERK), and SC79 (the activator of Akt) were used to uncover that fibulin-5 induced apoptosis through the ROS/mitogen-activated protein kinase and Akt signal pathways by downregulating TRPV1. Together, these results suggest that fibulin-5 might serve as a novel drug target for the treatment of CRC patients.