Upregulation of COPB2 Promotes Prostate Cancer Proliferation and Invasion Through the MAPK/TGF-β Signaling Pathway

Abstract

There is increasing evidence that coatomer protein complex subunit beta 2 (COPB2) plays an important role in various cancer types. This study explored the role and the downstream mediators of COPB2 in prostate cancer (PCa). The expression of COPB2 was determined by the Cancer Genome Atlas database and enzyme-linked immunosorbent assay. COPB2 expression was upregulated in PCa tissues and correlated with Gleason score, biochemical recurrence, and poor prognosis. The functional roles of COPB2 in PCa were verified through a series of experiments. Knocking down COPB2 expression inhibited the growth and clonogenesis of PCa cells, promoted cell apoptosis, and inhibited the ability of scratch repair, invasion of PCa cells, and tumor growth in Nude mice. To analyze downstream signaling pathways, ingenuity pathway analysis, GSEA, and whole-genome expression spectrum GeneChip analysis were used. Western blot revealed that COPB2 expression promoted the proliferation and invasion of PCa cells by regulating the MAPK/TGF-β signaling pathway. The interacting protein (nuclear protein 1, NUPR1) was identified via Co-IP, real-time PCR, Western blot, and TCGA database in sampled tissues. The expressions of the interaction proteins NUPR1 and COPB2 were negatively regulated by each other. COPB2 could be a new biomarker for PCa diagnosis and monitoring and to provide a theoretical basis for identifying effective drug intervention targets through in-depth mechanistic studies.

Candidate biomarkers for diagnosis and prognosis of prostate cancer based on bioinformatics methods

“…The TGF-beta signaling pathway plays an important role in the proliferation and migration of PCa, and can be blocked by TGF-beta receptor inhibitors to slow down the PCaproliferation and migration [24][25][26].…”

The role of CaMKK2 in Golgi-associated vesicle trafficking

“…Given the significant literature on the role of AMPK and CAMKIV activities on metabolic regulation, and their established status as CaMKK2 substrates, many of the biological effects of CaMKK2 on cancer have been attributed to this relationship. Our recent study suggests that there are fundamental roles for CaMKK2 as a regulator of membrane trafficking that can have equally profound effects on the metabolic and hence the proliferative capacity of cancer cells [ 25 , 97 , 98 ]. We know from the work of Michael White and others that COPI coatomer expression and retrograde Golgi trafficking sustains lysosomal activity and metabolic function in LKB1-mutant lung cancers [ 88 , 99 ].…”