ArticleOncogene2018
PHLPP2 stabilization by p27 mediates its inhibition of bladder cancer invasion by promoting autophagic degradation of MMP2 protein.
Article in Oncogene, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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Who cites it
25 citing papers in PubMed, 34 citations in OpenAlex.
- p27 specifically decreases in squamous carcinoma, and mediates NNK-induced transformation of human bronchial epithelial cells.Journal of cellular and molecular medicine · 2024Article
- PHLPP2: A Prognostic Biomarker in Adenocarcinoma of the Rectum.The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2023Article
- Cordycepin attenuates migration and invasion of HSC-4 oral squamous carcinoma cells through autophagy-dependent FAK/Akt and MMP2/MMP9 suppression.Journal of dental sciences · 2022Article
- Nuclear Vav3 is required for polycomb repression complex-1 activity in B-cell lymphoblastic leukemogenesis.Nature communications · 2022Article
- TRIM46 activates AKT/HK2 signaling by modifying PHLPP2 ubiquitylation to promote glycolysis and chemoresistance of lung cancer cells.Cell death & disease · 2022Article
- PLHPP2 inhibits the stemness of colorectal cancer by inactivating the Nrf2 signaling pathway.Journal of Cancer · 2022Article
- The Important Double-Edged Role of Astrocytes in Neurovascular Unit After Ischemic Stroke.Frontiers in aging neuroscience · 2022Review
- p27Cells · 2021Review
- LncRNA LOC729178 acts as a sponge of miR-144-3p to mitigate cigarette smoke extract-induced inflammatory injury via regulating PHLPP2 in 16HBE cells.Journal of molecular histology · 2021Article
- Oncogenic role ofAutophagy · 2021Article
- Phosphorylation of PED/PEA-15 at Ser116 and phosphorylation of p27 at Thr187 indicates a poor prognosis in hepatocellular carcinoma.Oncology letters · 2021Article
- Contrast effects of autophagy in the treatment of bladder cancer.Experimental biology and medicine (Maywood, N.J.) · 2021Review
- Prognostic Value of an Immunohistochemical Signature in Patients With Bladder Cancer Undergoing Radical Cystectomy.Frontiers in oncology · 2021Article
- Colonic Epithelial PHLPP2 Deficiency Promotes Colonic Epithelial Pyroptosis by Activating the NF-Oxidative medicine and cellular longevity · 2021Article
- MiRNA-516a promotes bladder cancer metastasis by inhibiting MMP9 protein degradation via the AKT/FOXO3A/SMURF1 axis.Clinical and translational medicine · 2020Article
- lncRNA SNHG1 Promotes Basal Bladder Cancer Invasion via Interaction with PP2A Catalytic Subunit and Induction of Autophagy.Molecular therapy. Nucleic acids · 2020Article
- Differential Expression and miRNA-Gene Interactions in Early and Late Mild Cognitive Impairment.Biology · 2020Article
- The inhibitory effect of compound ChlA-F on human bladder cancer cell invasion can be attributed to its blockage of SOX2 protein.Cell death and differentiation · 2020Article
- Article
- XIAP Interaction with E2F1 and Sp1 via its BIR2 and BIR3 domains specific activated MMP2 to promote bladder cancer invasion.Oncogenesis · 2019Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Pleckstrin homology domain leucine-rich repeat protein phosphatase 2 (PHLPP2) is a tumor suppressor that catalyzes the de-phosphorylation of the AGC kinases, while p27 acts as a tumor suppressor that regulates cell cycle, apoptosis, and cell motility. Our previous studies have identified that PHLPP2 participates in inhibition of transformation of human bronchial epithelial cells following lung carcinogen B[a]P/B[a]PDE exposure. However, nothing was known about the association of p27 with regulation of PHLPP2 expression and the role of PHLPP2 in bladder cancer (BC) invasion. In our current studies, we demonstrated that PHLPP2 inhibited BC invasion through promoting MMP2 degradation via p62-mediated autophagy; and p27 expression was able to stabilize PHLPP2 protein by inhibiting protein degradation of Hsp90, which could directly bind to PHLPP2 and protect it from degradation. More in-depth studies discovered that stabilization of Hsp90 by p27 was mediated by calpain1 proteolysis system, whereas p27 inhibited calpain1 gene transcription by attenuating Jak1/Stat1 cascade in human invasive BC cells. Collectively, we for the first time revealed PHLPP2 downregulation in BCs and its participating in promotion of BC invasion, as well as novel role of p27 and mechanisms underlying its regulation of PHLPP2 protein degradation through Hsp90-dependent manner. Our findings improve our understanding of p27 and PHLPP2 roles and their crosstalk in regulation of BC invasion, which further contributes to improve the current strategy for invasive bladder cancer therapy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.