CD147 modulates autophagy through the PI3K/Akt/mTOR pathway in human prostate cancer PC-3 cells

Abstract

The multifunctional glycoprotein cluster of differentiation (CD)147 is highly expressed on the cell surface of the majority of cancer cells, and promotes tumor invasion, metastasis and growth. However, the role of CD147 in autophagy has not yet been explored in prostrate cancer cells. In the present study, prostate cancer PC-3 cells were cultured under starvation conditions, and the expression level of CD147 gradually increased. Therefore, RNA interference was used to inhibit CD147 expression, in order to investigate the biological role of this glycoprotein in autophagy progression. Autophagic activity was monitored by the changes in green fluorescent protein-light chain 3 (GFP-LC3) location and the expression of the autophagy-associated protein LC3-II. It was found that downregulation of CD147 significantly promoted GFP-LC3 puncta formation and the expression of LC3-II. Furthermore, the levels of phosphorylated serine/threonine protein kinase B (p-Akt) and phosphorylated mammalian target of rapamycin (p-mTOR) were significantly decreased, and the level of LC3-II was inversely associated with levels of p-Akt and p-mTOR in cells with downregulated expression of CD147. The results of a trypan blue exclusion assay revealed that starvation-induced cell death was increased in PC-3/shCD147 cells compared with control PC-3/Scramble cells (37.7±6.4 vs. 21.7±5.5%). Together, these results indicate that CD147 may be important in the inhibition of autophagy via the PI3K/Akt/mTOR pathway, which prevents cell death from unrestrained autophagy.

Thapsigargin induces apoptosis of prostate cancer through cofilin‑1 and paxillin

“…The mTOR signal transduction pathway primarily participates in the synthesis of proteins (20). A previous study concerning the suspected associations between single nucleotide polymorphisms in the signal transduction pathway gene and prostate cancer conducted worldwide (21). The mTOR signaling pathway is an important therapeutic target of prostate cancer (21).…”

“…A previous study concerning the suspected associations between single nucleotide polymorphisms in the signal transduction pathway gene and prostate cancer conducted worldwide (21). The mTOR signaling pathway is an important therapeutic target of prostate cancer (21). mTOR is a highly conserved serine/threonine kinase, belonging to the phosphoinositide 3-kinase (PI3K) family, and is also the downstream effector of the PI3K/Akt signaling pathway (21).…”

“…The mTOR signaling pathway is an important therapeutic target of prostate cancer (21). mTOR is a highly conserved serine/threonine kinase, belonging to the phosphoinositide 3-kinase (PI3K) family, and is also the downstream effector of the PI3K/Akt signaling pathway (21). mTOR is widely expressed in cells and regulates multiple cellular functions in different cells, including survival and proliferation (21).…”

CD147 modulates androgen receptor activity through the Akt/Gsk-3β/β-catenin/AR pathway in prostate cancer cells

“…Dysregulation of the PI3K/Akt pathway promotes tumorigenesis and angiogenesis in various cancer types (18). Our prior study demonstrated that CD147 activates the class I PI3K/Akt pathway in prostate cells (15). GSK-3β also serves an important role in suppressing tumor progression through the cytoplasmic phosphorylation and degradation of β-catenin via the Akt signaling pathway (22).…”

“…C D147, a lso k now n a s ext r a c el lu la r mat r i x metalloproteinase inducer (EMMPRIN), is highly expressed on the surface of the majority of cancer cells (11). During tumorigenesis, CD147 contributes to metastasis, drug resistance and angiogenesis (12)(13)(14) invasion, metastasis and autophagy (12,15). In addition, CD147 regulates the canonical Wnt/β-catenin signaling pathway to accelerate lung tumorigenesis (16).…”