Abstract:
:Epithelial-to-mesenchymal transition (EMT) is controlled by cellular signaling pathways that trigger the loss of cell-cell adhesion and lead to the restructuring of the cell cytoskeleton. Transforming growth factor β (TGF-β) has been shown to regulate cell plasticity through the phosphorylation of Par6 on a conserved serine residue (S345) by the type II TGF-β receptor. We show here that atypical protein kinase C (aPKC) is an essential component to this signaling pathway in non-small-cell lung cancer (NSCLC) cells. We show that the aPKC, PKCι, interacts with TGF-β receptors through Par6 and that these proteins localize to the leading edge of migrating cells. Furthermore, Par6 phosphorylation on serine 345 by TGF-β receptors is enhanced in the presence of aPKC. aPKC kinase activity, as well as an association with Par6, were found to be important for Par6 phosphorylation. In effect, small interfering RNA-targeting aPKC reduces TGF-β-induced RhoA and E-cadherin loss, cell morphology changes, stress fiber production, and the migration of NSCLC cells. Interestingly, reintroduction of a phosphomimetic Par6 (Par6-S345E) into aPKC-silenced cells rescues both RhoA and E-cadherin loss with TGF-β stimulation. In conclusion, our results suggest that aPKCs cooperate with TGF-β receptors to regulate phospho-Par6-dependent EMT and cell migration.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Gunaratne A,Thai BL,Di Guglielmo GMdoi
10.1128/MCB.00837-12subject
Has Abstractpub_date
2013-03-01 00:00:00pages
874-86issue
5eissn
0270-7306issn
1098-5549pii
MCB.00837-12journal_volume
33pub_type
杂志文章abstract::We have isolated and subcloned three separate segments of human DNA which share strong sequence homology with a previously sequenced gene encoding a type I keratin, K14 (50 kilodaltons). Restriction endonuclease mapping has demonstrated that these three genes are tightly linked chromosomally, whereas the K14 gene appe...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.6.2.539
更新日期:1986-02-01 00:00:00
abstract::First characterized in Trypanosoma brucei, the spliced leader-associated (SLA) RNA gene locus has now been isolated from the kinetoplastids Leishmania tarentolae and Trypanosoma cruzi. In addition to the T. brucei SLA RNA, both L. tarentolae and T. cruzi SLA RNA repeat units also yield RNAs of 75 or 76 nucleotides (nt...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.18.8.4409
更新日期:1998-08-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.8.1.284
更新日期:1988-01-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.19.12.8451
更新日期:1999-12-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00327-10
更新日期:2010-09-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.24.9.3747-3756.2004
更新日期:2004-05-01 00:00:00
abstract::The first processing step in the maturation of mouse precursor rRNA involves cleavage at nucleotide ca. +650, at the 5' border of a 200-nucleotide region that is conserved across mammals and contains the sequences that direct the processing. To identify the relevant sequence elements, we used rRNAs with small internal...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.11.1.458
更新日期:1991-01-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00553-09
更新日期:2009-09-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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更新日期:2017-12-29 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.7.10.3842
更新日期:1987-10-01 00:00:00
abstract::Aberrant activation of the Wnt/β-catenin pathway and polo-like kinase 1 (Plk1) overexpression represent two common events in prostate cancer with relevant functional implications. This minireview analyzes their potential therapeutic significance in prostate cancer based on their role as androgen receptor (AR) signalin...
journal_title:Molecular and cellular biology
pub_type: 杂志文章,评审
doi:10.1128/MCB.00130-16
更新日期:2016-05-31 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00313-06
更新日期:2006-08-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.16.11.6516
更新日期:1996-11-01 00:00:00
abstract::Gap junctional intercellular communication is inhibited in response to tumor promoters and oncogene transformation, suggesting that loss of this function is an important step in tumor formation. To elucidate the molecular mechanisms responsible for this inhibition, we examined the expression of gap junction proteins a...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.11.10.5364
更新日期:1991-10-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00807-10
更新日期:2010-11-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01469-10
更新日期:2011-05-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.20.7.2358-2366.2000
更新日期:2000-04-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.17.8.4230
更新日期:1997-08-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.20.20.7427-7437.2000
更新日期:2000-10-01 00:00:00
abstract::The expression of three different actin genes in the sea urchin, Strongylocentrotus purpuratus, was monitored in embryos and adult tissues by using untranslated mRNA sequences as specific hybridization probes. Three distinct patterns of expression were found: muscle specific, embryo specific, and constitutive (i.e., p...
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pub_type: 杂志文章
doi:10.1128/mcb.4.5.840
更新日期:1984-05-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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更新日期:1987-10-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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更新日期:2013-11-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.7.2.672
更新日期:1987-02-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.23.7.2600-2607.2003
更新日期:2003-04-01 00:00:00
abstract::The p53 tumor suppressor gene product is a sequence-specific DNA-binding protein that is necessary for the G1 arrest of many cell types. Consistent with its role as a cell cycle checkpoint factor, p53 has been shown to be capable of both transcriptional activation and repression. Here we show a new potential role for ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.15.12.6554
更新日期:1995-12-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.5.9.2349
更新日期:1985-09-01 00:00:00
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pub_type: 杂志文章
doi:10.1128/mcb.8.8.3332
更新日期:1988-08-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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更新日期:2001-02-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.15.2.964
更新日期:1995-02-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.12.8.3346
更新日期:1992-08-01 00:00:00