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.
journal_name
Oncogenejournal_title
Oncogeneauthors
Peng M,Wang J,Zhang D,Jin H,Li J,Wu XR,Huang Cdoi
10.1038/s41388-018-0374-1subject
Has Abstractpub_date
2018-10-01 00:00:00pages
5735-5748issue
43eissn
0950-9232issn
1476-5594pii
10.1038/s41388-018-0374-1journal_volume
37pub_type
杂志文章相关文献
ONCOGENE文献大全abstract::The t(2;5) chromosomal translocation occurs in anaplastic large-cell lymphoma arising from activated T lymphocytes. This genomic rearrangement generates the nucleophosmin (NPM)-anaplastic lymphoma kinase (ALK) oncoprotein that is a chimeric protein consisting of parts of the nuclear protein NPM and ALK receptor protei...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1210095
更新日期:2007-05-03 00:00:00
abstract::The serine threonine checkpoint kinase 2 (CHK2) is a critical protein involved in the DNA damage-response pathway, which is activated by phosphorylation inducing cellular response such as DNA repair, cell-cycle regulation or apoptosis. Although CHK2 activation mechanisms have been amply described, very little is known...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2015.495
更新日期:2016-08-18 00:00:00
abstract::c-Myc drives uncontrolled cell proliferation in various human cancers. However, in mouse embryo fibroblasts (MEFs), c-Myc also induces apoptosis by activating the p19Arf tumor suppressor pathway. Tbx2, a transcriptional repressor of p19Arf, can collaborate with c-Myc by suppressing apoptosis. MEFs overexpressing c-Myc...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2008.294
更新日期:2008-11-20 00:00:00
abstract::Non-small cell lung cancer (NSCLC) is one of the most common and malignant carcinoma worldwide, and the incidence and mortality are increasing rapidly. Immunotherapy targeting programmed death 1/programmed death ligand 1 (PD-L1) signaling has shown prominent clinical effects in treating NSCLC; however, a poor understa...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2017.217
更新日期:2017-11-09 00:00:00
abstract::Survivin is a member of the inhibitor of apoptosis protein family and has an essential role in mitosis. Survivin is overexpressed in a large variety of human cancers and represents an attractive target for cancer therapy. Epidermal growth factor receptor and Her/neu-transformed human tumors in particular exhibit high ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2011.377
更新日期:2012-04-12 00:00:00
abstract::Acute myeloid leukemia (AML) is a heterogeneous disease comprising a large number of subtypes defined by specific chromosome abnormalities. One such subtype carries the t(6;9)(p22;q34) chromosome rearrangement, which leads to expression of the DEK-NUP214 chimeric gene, and has a particularly poor outcome. To provide a...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2016.118
更新日期:2016-10-27 00:00:00
abstract::Transcription factors (TFs) coordinate the on-and-off states of gene expression typically in a combinatorial fashion. Studies from embryonic stem cells and other cell types have revealed that a clique of self-regulated core TFs control cell identity and cell state. These core TFs form interconnected feed-forward trans...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/s41388-020-01459-w
更新日期:2020-10-01 00:00:00
abstract::To investigate a possible role for c-Jun homodimers in c-Jun-mediated transformation, we designed two chimeric c-Jun derivatives, called c-Juneb1 and c-Jungcn4. In these chimeric derivatives the natural dimerization domain of c-Jun was replaced by the heterologous homodimerization domain of the Epstein-Barr virus EB1 ...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1993-05-01 00:00:00
abstract::The marine alkaloid ascididemin (ASC) was shown to exert cytotoxicity even against multidrug-resistant cancer cells. Here, we address the signaling pathways utilized by ASC to trigger apoptosis in Jurkat leukemia T cells. We show that ASC (0.5-20 microM) induces a mitochondrial pathway that requires the activation of ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1207281
更新日期:2004-02-26 00:00:00
abstract::A single heat shock factor (HSF), mediating the heat shock response, exists from yeast to Drosophila, whereas several related HSFs have been found in mammals. This raises the question of the specific or redundant functions of the different members of the HSF family and in particular of HSF1 and HSF2, which are both ub...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2010.171
更新日期:2010-07-22 00:00:00
abstract::For many years the precise genetic etiology of the majority of Wilms' tumors has remained unexplained. Recently, the WTX gene, mapped to chromosome Xq11.1, has been reported to be lost or mutated in approximately one-third of Wilms' tumors. Moreover, in female cases, the somatically inactivated alleles were found to i...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2008.93
更新日期:2008-07-31 00:00:00
abstract::Here we show that pemetrexed-treated mesothelioma cells undergo accelerated senescence. This is characterized by the secretion of proinflammatory and mitogenic cytokines, reminiscent of an SASP (senescence-associated secretory phenotype). Conditioned media from senescent MPM (malignant pleural mesothelioma) cells trig...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2011.485
更新日期:2012-06-28 00:00:00
abstract::The steady-state levels of p53 mRNA and protein were barely detectable by Northern and Western blot analysis in spontaneously immortalized (10)3 and (10)7 murine embryo fibroblast (MEF) cells. But when cells were treated with cycloheximide (CHX) or emetine, expression levels were restored to those observed in primary ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1204423
更新日期:2001-05-31 00:00:00
abstract::After publication of this Article, the Authors noticed errors in some of the Figures. In Figures 2e, 2f-g, 4a, 4j, 5a and 6b, unmatched β-actin was inadvertently used as loading control for the immunoblots. These have been corrected using repeat data from a similar set of samples and the revised Figures containing mat...
journal_title:Oncogene
pub_type: 已发布勘误
doi:10.1038/s41388-020-1283-7
更新日期:2020-10-01 00:00:00
abstract::Normal human melanocytes are interspersed singly among keratinocytes along the basement membrane of the epidermis, whereas melanoma cells readily adhere to each other during invasion of the dermis or distant organs. The tumorigenic and metastatic phenotype of melanoma cells often correlates with increased expression o...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1204616
更新日期:2001-08-02 00:00:00
abstract::The mammalian target of rapamycin (mTOR) is a highly conserved serine-threonine kinase activated in response to growth factors and nutrients. Because of frequent dysregulation of the mTOR signaling pathway in diverse human cancers, this kinase is a key therapeutic target. Redd1 is a negative regulator of mTOR, mediati...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2011.102
更新日期:2011-09-01 00:00:00
abstract::We have isolated a human cDNA clone encoding a novel protein of 22 kDa that is a human counterpart of the rat oncoprotein PTTG. We show that the corresponding gene (hpttg) is overexpressed in Jurkat cells (a human T lymphoma cell line) and in samples from patients with different kinds of hematopoietic malignancies. An...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1202140
更新日期:1998-10-29 00:00:00
abstract::Epithelial-to-mesenchymal transition (EMT) promotes cell motility, which is important for the metastasis of malignant cells, and blocks CD95-mediated apoptotic signaling triggered by immune cells and chemotherapeutic regimens. CD95L, the cognate ligand of CD95, can be cleaved by metalloproteases and released as a solu...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2014.55
更新日期:2015-02-19 00:00:00
abstract::Sp1 is important for the transcription of many genes. Our previous studies have shown that Sp1 is degraded in normal cell, but it is preserved in cancer cells during mitosis and exists a priori in the daughter cells, ready to engage in gene transcription and thereby contributes to the proliferation and survival of can...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2011.649
更新日期:2012-11-22 00:00:00
abstract::The overexpression or mutation of tyrosine kinases (TKs), such as the epidermal growth factor receptor (EGFR), can lead to the development of cancer. The most common mutation of the EGFR in glioblastomas is the deletion of exons 2-7 known as the EGFRvIII. This mutant receptor cannot bind EGF but, instead, is constitut...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1209662
更新日期:2006-10-19 00:00:00
abstract::Amplified segments of the long arm of chromosome 12 are frequently observed in human sarcomas. In most cases there are separate amplified regions around the MDM2 and CDK4 genes. Here we show recurrent amplification of a third region encompassing HMGIC, a human architectural transcription factor gene. Reduced amplifica...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201135
更新日期:1997-06-19 00:00:00
abstract::A dominant negative mutant of Ras, M17 Ras, was used to study the role of Ras in receptor coupling of Raf-1 and B-Raf protein serine/threonine kinases (PSKs). We found that mutant Ras blocks serum- and 12-O-tetradecanoyl phorbol 13-acetate-induced activation of Raf-1 kinase in NIH3T3 cells and Raf-1 as well as B-Raf P...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1992-09-01 00:00:00
abstract::Dysregulation of cellular signaling pathways can lead to colon cancer. However, research on the key signaling effectors or regulators in colon carcinogenesis is limited. Casein kinase-2 interacting protein-1 (CKIP-1; also known as PLEKHO1) is crucial during adult bone formation and is a promising drug target for osteo...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2013.340
更新日期:2014-07-10 00:00:00
abstract::Targeted cancer therapies, although often effective, have limited utility owing to preexisting primary or acquired secondary resistance. Consequently, agents are sometimes used in combination to simultaneously affect multiple targets. MicroRNA mimics are excellent therapeutic candidates because of their ability to rep...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2014.282
更新日期:2015-07-01 00:00:00
abstract::Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and comprises two major histological subtypes: alveolar rhabdomyosarcoma (ARMS) and embryonal rhabdomyosarcoma (ERMS). Seventy-five percent of ARMS harbor reciprocal chromosomal translocations leading to fusion genes of the forkhead transcriptio...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2010.368
更新日期:2010-12-02 00:00:00
abstract::Glycolysis is critical for cancer stem cell reprogramming; however, the underlying regulatory mechanisms remain elusive. Here, we show that pyruvate dehydrogenase kinase 1 (PDK1) is enriched in breast cancer stem cells (BCSCs), whereas depletion of PDK1 remarkably diminishes ALDH+ subpopulations, decreases stemness-re...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2017.368
更新日期:2018-02-22 00:00:00
abstract::One of the key events in tumor initiation in mouse skin is mutational activation of the H-ras gene. Papillomas induced by the most carcinogenic environmental polycyclic aromatic hydrocarbon (PAH), dibenzo[a,l]pyrene (DB[a,l]P), in SENCAR mouse skin contain a specific H-ras codon 61 (CAA-->CTA) mutation. We describe he...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201853
更新日期:1998-06-18 00:00:00
abstract::The tumor microenvironment plays a critical role in prostate cancer (PC) development and progression. Inappropriate activation of the stroma potentiates the growth and transformation of epithelial tumor cells. Here, we show that upregulation of monoamine oxidase A (MAOA), a mitochondrial enzyme that degrades monoamine...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-020-1217-4
更新日期:2020-04-01 00:00:00
abstract::The MLL (HRX/ALL-1 gene is frequently disrupted in infantile leukemias and therapy-related leukemias and fused to various translocation partner genes. We previously showed that chimeric MLL proteins localize in the nuclei in a fashion similar to that of MLL protein even if the partner gene encodes a cytoplasmic protei...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1202400
更新日期:1999-01-28 00:00:00
abstract::The relevance of potentially reversible post-translational modifications required for controlling cellular processes in cancer is one of the most thriving arenas of cellular and molecular biology. Any alteration in the balanced equilibrium between kinases and phosphatases may result in development and progression of v...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/onc.2013.80
更新日期:2014-02-20 00:00:00