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.
Highlights
Autophagy is an intracellular lysosomal degradation process that facilitates the proteolytic degradation of cell contents to generate small reusable biomolecules
During the induction of starvation, increased LC3‐II was observed in PC‐3/shCD147 cells compared with the control PC‐3/Scramble cells (P
To investigate the effect of the phosphoinositide 3‐kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway in the regulation of autophagy induced by CD147, the expression levels of p‐Akt, phosphorylated mammalian target of rapamycin (p‐mTOR) and LC3‐II were examined in the transfected PC‐3 cells that were cultured with or without 20 μM LY294002, a specific inhibitor of Class I PI3K
Summary
Autophagy is an intracellular lysosomal degradation process that facilitates the proteolytic degradation of cell contents to generate small reusable biomolecules. Autophagy plays a role in a wide variety of physiological and pathological processes, including adaption to starvation [1], embryonic development [2], cell survival and death [3], and tumor suppression [4]. Previous studies revealed that CD147 plays an important role in the invasion and metastasis of prostate cancer by inducing matrix metalloproteinase 2 (MMP2) and MMP9 secretion [12,13,14]. Metastasis and invasion is regulated by the PI3K/Akt signaling pathway [15]. It was hypothesized that the PI3K/Akt pathway may be involved in the regulation of autophagy by CD147. The present study investigates the association between CD147 and autophagy, and the potential molecular mechanisms in prostate cancer PC‐3 cells
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