C5a promotes the proliferation of human nasopharyngeal carcinoma cells through PCAF-mediated STAT3 acetylation

Abstract

The anaphylatoxin C5a is a chemoattractant that can induce various inflammatory responses in vivo via the C5a receptor (C5aR). There is emerging evidence that C5a is generated in the cancer microenvironment. However, the role of C5a in human nasopharyngeal carcinoma (NPC) remains largely unclear. Thus, the present study aimed to examine the direct influence of C5a stimulation on the proliferation of human NPC cells and to identify the underlying molecular mechanisms. The effects of C5a stimulation on the proliferation of human NPC cells were studied in vitro, and P300/CBP-associated factor (PCAF)‑mediated signal transducer and activator of transcription 3 (STAT3) acetylation and its role in regulating the proliferation of NPC cells was subsequently explored. Our results demonstrated that C5a stimulation increased the proliferation of human NPC cells in vitro. STAT3 acetylation was further found to be enhanced in human NPC cells induced by C5a. Moreover, PCAF induction was required for STAT3 acetylation in human NPC cells by exposure to C5a. Functionally, PCAF-mediated STAT3 acetylation contributed to the proliferation of human NPC cells stimulated by C5a. These results illustrate the novel activity of the C5a-C5aR axis that promotes human NPC cell proliferation through PCAF‑mediated STAT3 acetylation. This may provide a potential strategy for treating human NPC through inhibition of C5a or its receptors.

Loss of Elp3 Impairs the Acetylation and Distribution of Connexin-43 in the Developing Cerebral Cortex

“…Similar to Elp3, PCAF has been shown to acetylate non-histones proteins such as β-catenin (Ge et al, 2009), Akt1 (Zhang et al, 2015), Stat3 (Cai et al, 2014) and lin28 (Wang et al, 2014). It would be interesting to test whether PCAF is also involved in the regulation of Cx43 acetylation in the developing cortex.…”

IL-17A promotes the proliferation of human nasopharyngeal carcinoma cells through p300-mediated Akt1 acetylation

“…NPC cells were transfected with pcDNA3.1/Akt1-His or pGCsi-U6/neo/GFP using Lipofectamine 2000 according to a previously described method (28). Cells were seeded into 6-well plates at a density of 1×10 5 cells/well.…”

“…For certain studies, co-immunoprecipitation experiments were performed using an antibody against t-Akt1 according to a previously described method (28). …”

“…Western blot analysis was performed to detect β-actin, CBP, p300, PCAF, t-Akt1, p-Akt-Thr 308 , p-Akt-Ser 473 and acetylated-lysine, according to a previously described method (28). …”

Innate immune mediators in cancer: between defense and resistance

“…Whereas gC1qR promoted angiogenesis and tumor growth, cC1qR stimulated the phagocytosis of tumor cells and was detrimental to tumor growth . Moreover, C1q was able to promote angiogenesis, as well as adhesion, proliferation, and metastasis of melanoma tumor cells independently of complement activation . The importance of other complement components in tumor biology was elegantly demonstrated by Bonavita et al., who reported that the pentraxin‐related protein PTX3 acts as an oncosuppressor regulating complement‐associated inflammation in cancer.…”