Deficiency of pigment epithelium-derived factor in nasopharyngeal carcinoma cells triggers the epithelial–mesenchymal transition and metastasis

Abstract

Distant metastasis is the primary cause of nasopharyngeal carcinoma (NPC) treatment failure while epithelial–mesenchymal transition (EMT) is the critical process of NPC invasion and metastasis. However, tumor-suppressor genes involved in the EMT and metastasis of NPC have not been explored clearly compared with the oncogenes. In the present study, the expression of pigment epithelium-derived factor (PEDF), a potent endogenous antitumor factor, was diminished in human NPC tissues and associated with clinicopathological and EMT features. The knockdown of PEDF induced EMT in lower metastatic NPC cell lines and overexpression of PEDF restored epithelial phenotype in higher metastatic NPC cell lines with typical EMT. The inhibition of PEDF mediated NPC cell spontaneous metastasis in vivo. LRP6/GSK3β/β-catenin signal pathway rather than AKT/GSK3β pathway was involved in the effects of PEDF on EMT. The expression of PEDF was directly downregulated by elevated miR-320c in NPC. In conclusion, our findings indicate for the first time that PEDF functions as tumor-suppressor gene in the occurrence of EMT and metastasis in NPC. PEDF could serve as a promising candidate for NPC diagnosis, prognosis and treatment.

Pigment Epithelium-Derived Factor Plays a Role in Alzheimer's Disease by Negatively Regulating Aβ42

“…Interestingly, both diabetes and cancer are age-related diseases [ 22 – 25 ]. PEDF levels are decreased in the retina of diabetic patients and in multiple cancers according to our previous reports [ 26 – 28 ]. It is well known that age is a major risk factor for AD, with a doubling of risk every 5 years in individuals over 65 years of age [ 29 , 30 ].…”

“…PEDF is a multifunctional protein characterized by its broad functions, including anti-inflammation [ 42 ], antiangiogenesis [ 43 ], antitumorigenesis [ 27 ], and antimetastasis [ 26 , 44 ] activities. Previous studies including ours have demonstrated that PEDF can be expressed in almost all tissues and different cell types containing liver, adipose, epithelial cells, endothelial cells, neurons, etc.…”

“…For cell immunofluorescence, cells were plated on culture slides and then fixed in ice-cold 4% paraformaldehyde for 30 min. Then, the samples were prepared according to the protocol as described previously [ 26 ]. The slices were visualized under a confocal microscope (Axio Observer Z1, ZEISS, Jena, Germany).…”

Curcumol attenuates epithelial-mesenchymal transition of nasopharyngeal carcinoma cells via TGF-β1

“…It has been demonstrated that an increase in the expression of miR-9-3p suppresses the metastasis of NPC via inhibition of the EMT process, thereby providing a series of therapeutic targets for the treatment of NPC ( 10 ). Pigment epithelium-derived factor functions as a tumor-suppressor gene in the occurrence of EMT and metastasis in NPC ( 11 ). Thus, investigation of therapeutic approaches targeting EMT pathways may be promising for patients with NPC.…”

FUBP1 promotes neuroblastoma proliferation via enhancing glycolysis-a new possible marker of malignancy for neuroblastoma

“…Vectors encoding FUBP1 shRNAs were purchased from Hanbio Biotechnology (Shanghai, China) Co., Ltd. FUBP1 siRNA, HIF1α and control siRNA were purchased from RiboBio (Guangzhou, China). Plasmids encoding FUBP1 were purchased from Obio Technology (Shanghai, China) Corp, Ltd.; the lentiviruses were packaged, and cells were transduced and subjected to puromycin selection as previously described [35]. According to the manufacturer’s instructions, transfections were performed at approximately 60% confluency using RNAiMAX or Lipofectamine 2000 (Invitrogen, USA).…”