Glucose-regulated protein 78 contributes to the proliferation and tumorigenesis of human colorectal carcinoma via AKT and ERK pathways.

Glucose-regulated protein 78 (GRP78), a molecular chaperon in the endoplasmic reticulum (ER), is overexpressed in a variety of tumor types and plays a critical role in cancer cell proliferation, migration, invasion and drug resistance. However, the mechanisms underlying the role of GRP78 in tumor carcinogenesis remain largely unknown. In the present study, we found that GRP78 knockdown in colorectal carcinoma (CRC) cells significantly inhibited cell proliferation, colony formation and tumorigenesis in vitro and in vivo. The proliferation inhibition of CRC cells by GRP78 knockdown was associated with an S phase arrest, a reduced G1/S transition, and a downregulation of phosphorylation of AKT and ERK1/2, key cell cycle regulatory proteins. In addition, GRP78 knockdown enhanced the apoptosis induced by 5-fluorouracil (5-FU) in CRC cells. Taken together, our results indicate that GRP78 plays an important role in the development and progression of CRC and may have therapeutic potential for CRC patients.