Pinin promotes tumor progression via PI3K/AKT/CREB signaling pathway in prostate cancer

Abstract

<jats:title>Abstract</jats:title> <jats:p>Background 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. Methods The expression levels of PNN were assessed in prostate cancer by qRT-PCR, western blotting and immunohistochemical staining. The other proteins were quantified by western blotting. PNN-depleted cells were produced by infecting with lentivirus bearing short hairpin RNAs against PNN. PNN over-expression was performed by transfecting PNN expression vector. The proliferation of each cell line was assessed by MTS and colony formation assays. Tumors were induced on nude mice by injecting tumor cells subcutaneously. Apoptosis and cell cycle were evaluated by flow cytometry. Transwell and wound healing assay were performed to determined the ability of cell invasion and migration. The TCGA data were analyzed with GEPIA (Gene Expression Profiling Interactive Analysis) and GraphPad Prism. Results Here, 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 <jats:italic>in vitro</jats:italic> and <jats:italic>in vivo</jats:italic>, and might modulate 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 PI3K/AKT/CREB signaling, which was reversed by AKT and CREB inhibitors. Conclusions Collectively, these findings indicated that PNN plays important roles in prostate cancer tumorigenesis and progression and it may be a potential therapeutic target for prostate cancer treatment.</jats:p>

The prognostic effect of PNN in digestive tract cancers and its correlation with the tumor immune landscape in colon adenocarcinoma

“…Another study showed that PNN was upregulated in prostate cancer tissues and accelerated cell invasion with downregulation of E‐cadherin. A mechanistic study demonstrated that PNN promotes tumor proliferation by activating CREB via the PI3K/AKT and ERK/MAPK pathways 43 . In our study, the results of functional enrichment analysis demonstrated that PNN was involved in “spliceosome,” “Adherens junction,” and mRNA processing.” KEGG analysis showed that PNN affects cell–cell adhesion and tumor invasion and metastasis via a variety of signaling pathways (e.g., WNT signaling pathway, ErbB signaling pathway, and mTOR signaling pathway).…”

“…A mechanistic study demonstrated that PNN promotes tumor proliferation by activating CREB via the PI3K/AKT and ERK/MAPK pathways. 43 In our study, the results of functional enrichment analysis demonstrated that PNN was involved in “spliceosome,” “Adherens junction,” and mRNA processing.” KEGG analysis showed that PNN affects cell–cell adhesion and tumor invasion and metastasis via a variety of signaling pathways (e.g., WNT signaling pathway, ErbB signaling pathway, and mTOR signaling pathway). The WNT signaling pathway is known as one of the most important signaling pathways, and its activation is very common during the development of many tumors by facilitating cell differentiation, polarization, and migration.…”

“…A mechanistic study demonstrated that PNN promotes tumor proliferation by activating CREB via the PI3K/AKT and ERK/MAPK pathways. 43 In migration. 44 ErbB belongs to the receptor tyrosine kinase receptor family and includes four distinct members: EGFR (also known as ErbB-1/HER1), ErbB-2 (HER2), ErbB-3 (HER3), and ErbB-4 (HER4).…”

Transcriptomics analysis of gene expression in pulmonary arterial hypertension and identification of hub proteins

“…Involved in epithelia cell-cell attachment creation and maintenance. Renal cell carcinoma has a latent tumor suppressor (Meng et al, 2021).…”

Pinin Induces Epithelial-to-Mesenchymal Transition in Hepatocellular Carcinoma by Regulating m6A Modification

“…Shi et al found that Pinin may act as a tumor suppressor in certain types of cancers [ 21 ]. By contrast, some reports revealed that Pinin is an oncogene in colorectal cancer [ 22 ], nasopharyngeal carcinoma [ 23 ], renal cancer [ 24 ], and prostate cancer [ 25 ]. Yang et al stated that Pinin promotes cell proliferation and tumorigenesis in hepatocellular carcinoma (HCC) [ 26 ].…”