Platelet-activating factor receptor-mediated PI3K/AKT activation contributes to the malignant development of esophageal squamous cell carcinoma

J, Chen; Lan, Tian; Zhang, W; Dong, Lei; Kang, Nan; Zhang, S; Fu, Ming; Liu, B; Liu, K; Zhang, C; Hou, Jincai; Zhan, Qimin

doi:10.1038/onc.2014.434

Cited by 39 publications

(43 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…mTOR functions as an oncogene in many tumour types 27 28 29 , including NPC 30 . The PI3K/Akt signalling pathway controls fundamental cellular processes, such as cell survival, growth, proliferation, cell repair, cell migration and angiogenesis, and is constitutively activated in nearly all cancer types 31 32 33 . Activation of PI3K/Akt/mTOR signalling through mutation of pathway components as well as through activation of upstream signalling molecules occurs in a majority of cancers 34 35 .…”

Section: Disscussionmentioning

confidence: 99%

miR-3188 regulates nasopharyngeal carcinoma proliferation and chemosensitivity through a FOXO1-modulated positive feedback loop with mTOR–p-PI3K/AKT-c-JUN

et al. 2016

View full text Add to dashboard Cite

The biological role of miR-3188 has not yet been reported in the context of cancer. In this study, we observe that miR-3188 not only reduces cell-cycle transition and proliferation, but also significantly prolongs the survival time of tumour-bearing mice as well as sensitizes cells to 5-FU. Mechanistic analyses indicate that miR-3188 directly targets mTOR to inactivate p-PI3K/p-AKT/c-JUN and induces its own expression. This feedback loop further suppresses cell-cycle signalling through the p-PI3K/p-AKT/p-mTOR pathway. Interestingly, we also observe that miR-3188 direct targeting of mTOR is mediated by FOXO1 suppression of p-PI3K/p-AKT/c-JUN signalling. In clinical samples, reduced miR-3188 is an unfavourable factor and negatively correlates with mTOR and c-JUN levels but positively correlates with FOXO1 expression. Our studies demonstrate that as a tumour suppressor, miR-3188 directly targets mTOR to stimulate its own expression and participates in FOXO1-mediated repression of cell growth, tumorigenesis and NPC chemotherapy resistance.

show abstract

Section: Disscussionmentioning

confidence: 99%

miR-3188 regulates nasopharyngeal carcinoma proliferation and chemosensitivity through a FOXO1-modulated positive feedback loop with mTOR–p-PI3K/AKT-c-JUN

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Platelet-activating factor (PAR) receptor (PAFR) is one of GPCR, which can be activated by PAR. It has been reported to promote non-small cell lung cancer (NSCLC) progression and metastasis by initiating forward feedback loop between PAFR and STAT3 [10], and contributes to the malignant development of esophageal squamous cell carcinoma by stimulating PI3K/AKT activation [11]. PAFR can also induce chemotherapy resistance in ovarian cancer through transactivating of epidermal growth factor receptor (EGFR) [12, 13].…”

Section: Introductionmentioning

confidence: 99%

PAFR selectively mediates radioresistance and irradiation-induced autophagy suppression in prostate cancer cells

et al. 2017

View full text Add to dashboard Cite

Platelet-activating factor receptor (PAFR) promotes tumorigenesis, angiogenesis and metastasis. Here, we defined the PAFR as a yielding new inhibiting target to selectively enhance the sensitivity of prostate cancer (PCa) cells to radiation. The selective responding to PAFR inhibiter may be caused by the differential expression pattern of PAFR in PCa cells. In this study, we also determined PAFR as a molecular basis by which the radiation induces autophagy suppression independent of activating mTOR pathway. PAFR can bind to the autophagy-indispensable protein Beclin 1, leading to the disability in its serine phosphorylation. The PAFR antagonist Ginkgolide B (GB) can sensitize radiotherapy by disrupting the formation of PAFR/Beclin 1 complex in PC3 and LNCaP cells, which have elevated PAFR expression after radiation exposure. Most importantly, GB efficiently radiosensitized PC3 and LNCaP tumor xenografts in vivo, and significantly reduced tumor burden. Overall, our results elucidated a significant role of GB in selectively improving the outcomes of PCa receiving radiation therapy.

show abstract

“…The activated AKT can further phosphorylate BAD on Ser-136 and prompt it to dissociate from the Bcl-2/Bcl-xl complex, ultimately resisting cell apoptosis. The PI3K/AKT pathway has been proven to be related to the occurrence, progression, and prognosis of EC, as well as resistance to chemotherapy and radiotherapy [ 19 – 22 ]. Moreover, the inhibitor of the PI3K/Akt pathway significantly suppressed cell proliferation and induced cell apoptosis via suppressed Bcl-xl expression.…”

Section: Discussionmentioning

confidence: 99%

Synergistic anticancer effect of combined crocetin and cisplatin on KYSE-150 cells via p53/p21 pathway

Shen

Ouyang

et al. 2017

Cancer Cell Int

View full text Add to dashboard Cite

BackgroundMore than 400,000 patients die from esophageal cancer annually. Considerable efforts have been made to develop new and effective treatments, one of which is directed toward herbal medication. Crocetin is a natural carotenoid dicarboxylic acid isolated from the Chinese herb saffron. We recently reported on the anticancer effects of saffron. This study aimed to determine whether crocetin combined cisplatin has synergistic effect in KYSE-150 cells and explore the underlying mechanism.MethodsKYSE-150 cells were treated with crocetin and/or cisplatin. The effects on cell viability, cell apoptosis, mitochondrial membrane potential (MMP), as well as the expression levels of PI3K/AKT, MAPKs, p53/p21, and apoptosis-related protein were evaluated. MTT assay, Annexin V-FITC/PI staining, Rh123 staining, and Western blot analysis were used.ResultsThe cell proliferation significantly decreased and cell apoptosis was induced with combined crocetin and cisplatin, compared with either crocetin only or cisplatin only. The outcome suggested that crocetin combined cisplatin has synergistic effects on inhibition of cell proliferation and pro-apoptotic effect of cisplatin on KYSE-150 cells. Disruption of MMP, upregulation of cleaved caspase-3 expression, and downregulation of Bcl-2 occurred in the group treated with combined treatment. No significant differences in p-PI3K, p-AKT, and MAPKs activity were indicated between combined treatment group and the individual treatment group. However, the expression levels of p53 and p21 were markedly higher in the combined treatment group than in the individual treatment group. The wild-type p53 inhibitor, PFT-α suppressed the overexpression of p53/p21 and the synergistic effect induced by the combination of crocetin and cisplatin.ConclusionsWe concluded that crocetin combined with cisplatin exerts a synergistic anticancer effect by up-regulating the p53/p21 pathway.

show abstract

Platelet-activating factor receptor-mediated PI3K/AKT activation contributes to the malignant development of esophageal squamous cell carcinoma

Cited by 39 publications

References 49 publications

miR-3188 regulates nasopharyngeal carcinoma proliferation and chemosensitivity through a FOXO1-modulated positive feedback loop with mTOR–p-PI3K/AKT-c-JUN

miR-3188 regulates nasopharyngeal carcinoma proliferation and chemosensitivity through a FOXO1-modulated positive feedback loop with mTOR–p-PI3K/AKT-c-JUN

PAFR selectively mediates radioresistance and irradiation-induced autophagy suppression in prostate cancer cells

Synergistic anticancer effect of combined crocetin and cisplatin on KYSE-150 cells via p53/p21 pathway

Contact Info

Product

Resources

About