Platelet-activating factor receptor activation promotes prostate cancer cell growth, invasion and metastasis via ERK1/2 pathway

Abstract

Platelet-activating factor (PAF) and its receptor (PAFR), have been reported to participate in many cellular processes of cancer. However, little is known about their function in prostate cancer. In the present study, we found that PAFR was overexpressed in prostate cancer cells. PAF stimulation dose-dependently promoted the invasion, migration and growth of prostate cancer cells in vitro, while knockdown of PAFR inhibited the effect of PAF on prostate cancer cells. We further found that PAFR promoted prostate cancer cell growth and metastasis in vivo. Moreover, we found that PAFR activation increased MMP-3 expression and decreased E-cadherin expression of prostate cancer cells in vitro and in vivo. Finally, we found that PAFR time-dependently induced activation of ERK1/2, and ERK1/2 pathway contributed to PAFR-mediated prostate cancer cell invasion, migration and growth. Together, our findings demonstrate that PAFR can activate ERK1/2 pathway, and subsequently increase MMP-3 expression and decrease E-cadherin expression, which finally promote prostate cancer cell growth, invasion and metastasis. Thus, PAFR may act as a potential target for therapeutic use of prostate cancer.

WITHDRAWN: LPCAT1 promotes castration resistant prostate cancer progression by increasing PAF release and mRNA synthesis

“…Although PAF was reported to promote the migration and proliferation of breast cancer, esophageal squamous cell carcinoma and ovarian cancer mainly via activating PAFR signaling pathway [20], our previous studies [7] showed that PAF was only involved PC-3 cells invasion and migration. The increased or decreased invasion and migration of CRPC cells induced by LPCAT1 overexpression or silencing can be reversed by PAF pathway inhibition or exogenous PAF, respectively.…”

Inflammation, not Cholesterol, Is a Cause of Chronic Disease

“…New blood vessel formation penetrating solid tumours seems to be required for their growth and metastasis. Production of PAF and overexpression of PAF-R are implicated in the tumour-endothelium interplay during cancer growth, invasion, and metastasis in several types of cancer [ 57 , 114 , 169 , 170 , 171 ]. PAF and PAF-R are also involved in tumour growth that is associated with immunosuppression [ 172 , 173 , 174 ], while the crosstalk between PAF/PAF-R pathways and growth factors receptors pathways suggests a potentially important signalling link between inflammatory and growth factor signalling in cancer [ 173 , 174 , 175 ].…”

Effect of cell‐phone radiofrequency on angiogenesis and cell invasion in human head and neck cancer cells

“…1,4,5 More specifically, it has been reported that cell phone radiofrequency can damage DNA and deregulate gene expression of apoptotic and antiapoptotic pathways, including signal transducer and activator of transcription 3 (STAT3), tumor necrosis factor a, and interleukin-6 in brain cells. [17][18][19] Meanwhile, it is important to emphasize that STAT3 could also contribute in angiogenesis, cell invasion, and colony formation stimulation in our experimental models, because cell-phone radiofrequency is found to activate STAT3; and it has been reported that the STAT3 signaling pathway can enhance angiogenesis and downregulate E-cadherin, thereby enhancing cell invasion. 10 Nevertheless, there is no study about the outcome of cell-phone radiofrequency on human cancers' progression, including head and neck malignancy.…”

“…More significantly, we report that cell-phone radiofrequency can activate Erk1/ Erk2, which could be the main pathway behind the reduction of E-cadherin expression and consequent cell invasion stimulation; this is supported by several recent studies that point out that Erk1/Erk2 activation enhances cell invasion via the down-regulation of E-cadherin and up-regulation of matrix metalloproteinase, which are important controllers of cell invasion and metastatsis. [17][18][19] Meanwhile, it is important to emphasize that STAT3 could also contribute in angiogenesis, cell invasion, and colony formation stimulation in our experimental models, because cell-phone radiofrequency is found to activate STAT3; and it has been reported that the STAT3 signaling pathway can enhance angiogenesis and downregulate E-cadherin, thereby enhancing cell invasion. 16,20 In addition, tumor necrosis factor-a and interleukin-6 could present other links between cancer progression and cell-phone radiofrequency, as mentioned previously.…”