4.6 Article

Pinin promotes tumor progression via activating CREB through PI3K/AKT and ERK/MAPK pathway in prostate cancer

期刊

AMERICAN JOURNAL OF CANCER RESEARCH
卷 11, 期 4, 页码 1286-+

出版社

E-CENTURY PUBLISHING CORP

关键词

PNN; prostate cancer; tumor progression; CREB; PI3K/AKT; ERK/MAPK

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资金

  1. Natural Science Foundation of Zhejiang Province [LY20H050002, LQ20H160008, LY18H050003]
  2. Ningbo Natural Science Foundation [2018A610297, 202003N4259]
  3. Ningbo Science and Technology Planning Project [202002N3192]
  4. Fund of Ningbo Clinical Research Center for Urological Disease [2019A21001]

向作者/读者索取更多资源

PNN was found to be upregulated in prostate cancer tissues and play a crucial role in promoting cell growth, invasion, and migration through the activation of CREB. The effects of PNN on prostate cancer cells were mediated by the PI3K/AKT and ERK/MAPK pathways, indicating that PNN could be a potential therapeutic target for prostate cancer treatment.
Pinin (PNN), a desmosome associated protein, was demonstrated to be over-expressed and act as a tumor-promoting factor in ovarian cancer, hepatocellular carcinoma and colorectal cancer. However, the precise role of PNN in prostate cancer is still unknown. In the study, we reported that PNN was upregulated in prostate cancer tissues and PNN expression was positively associated with Gleason score, tumor stage and tumor metastasis. PNN promoted cell growth and tumorigenicity in vitro and in vivo, and modulated cell growth through driving G1/S transition via CDK6, CDK2, and Cyclin D1 in prostate cancer cells. Furthermore, PNN accelerated cell invasion, migration and EMT processes of prostate cancer cells, accompanied with the up-regulation of MMP-2, MMP-9, N-cadherin, Vimentin and down-regulation of E-cadherin. Mechanism study demonstrated that the proliferation-and motility promoting effects of PNN on prostate cancer cells dependent on the activation of CREB, which was reversed by CREB inhibition. More important, PNN activated CREB via PI3K/AKT and ERK/MAPK pathway. Collectively, these findings indicated that PNN plays important roles in prostate cancer tumorigenesis and progression and it is a potential therapeutic target for prostate cancer treatment.

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