DLC1 suppresses NF-[kappa]B activity in prostate cancer cells due to its stabilizing effect on adherens junctions

DLC1 (Deleted in Liver Cancer 1) gene encodes a RhoGTPase-activating protein (RhoGAP), which exerts most of its tumor suppressor functions through suppression of small Rho GTPases proteins RhoA, RhoB, RhoC and to some degree Cdc42, but not Rac. RhoGTPases are implicated in NF-[kappa]B activation in...

Full description

Saved in:
Bibliographic Details
Published inSpringerPlus Vol. 3; no. 1; p. 1
Main Authors Tripathi, Veenu, Popescu, Nicholas C, Zimonjic, Drazen B
Format Journal Article
LanguageEnglish
Published Heidelberg Springer Nature B.V 01.01.2014
Online AccessGet full text

Cover

Loading…
Abstract DLC1 (Deleted in Liver Cancer 1) gene encodes a RhoGTPase-activating protein (RhoGAP), which exerts most of its tumor suppressor functions through suppression of small Rho GTPases proteins RhoA, RhoB, RhoC and to some degree Cdc42, but not Rac. RhoGTPases are implicated in NF-[kappa]B activation in highly invasive prostate carcinoma (PCA), with consequences on cell proliferation, survival and metastatic capacity. Here we demonstrate that DLC1 transduction in two androgen-independent (AI) and highly metastatic PCA cell lines negatively regulates NF-[kappa]B activity in a GAP- and [alpha]-catenin-dependent manner. Expressed DLC1 protein suppresses the phosphorylation of NF-[kappa]B inhibitor, I[kappa]B[alpha], causes its relocation from membrane ruffles into cytoplasm and attenuates its ubiquitination and subsequent degradation. DLC1-mediated NF-kB suppression and its effects are comparable to NF-[kappa]B inhibition using either shRNA knockdown or peptide inhibitor. Expression of transduced DLC1 suppressed the expression of NF-[kappa]B mediated genes. Such effects were found to be reliant on presence of calcium, indicating that the observed modifications are dependent on, and enabled by DLC-mediated stabilization of adherens junctions. These results expand the multitude of DLC1 interactions with other genes that modulate its oncosuppressive function, and may have potential therapeutic implications.
AbstractList DLC1 (Deleted in Liver Cancer 1) gene encodes a RhoGTPase-activating protein (RhoGAP), which exerts most of its tumor suppressor functions through suppression of small Rho GTPases proteins RhoA, RhoB, RhoC and to some degree Cdc42, but not Rac. RhoGTPases are implicated in NF-[kappa]B activation in highly invasive prostate carcinoma (PCA), with consequences on cell proliferation, survival and metastatic capacity. Here we demonstrate that DLC1 transduction in two androgen-independent (AI) and highly metastatic PCA cell lines negatively regulates NF-[kappa]B activity in a GAP- and [alpha]-catenin-dependent manner. Expressed DLC1 protein suppresses the phosphorylation of NF-[kappa]B inhibitor, I[kappa]B[alpha], causes its relocation from membrane ruffles into cytoplasm and attenuates its ubiquitination and subsequent degradation. DLC1-mediated NF-kB suppression and its effects are comparable to NF-[kappa]B inhibition using either shRNA knockdown or peptide inhibitor. Expression of transduced DLC1 suppressed the expression of NF-[kappa]B mediated genes. Such effects were found to be reliant on presence of calcium, indicating that the observed modifications are dependent on, and enabled by DLC-mediated stabilization of adherens junctions. These results expand the multitude of DLC1 interactions with other genes that modulate its oncosuppressive function, and may have potential therapeutic implications.
Author Zimonjic, Drazen B
Tripathi, Veenu
Popescu, Nicholas C
Author_xml – sequence: 1
  givenname: Veenu
  surname: Tripathi
  fullname: Tripathi, Veenu
– sequence: 2
  givenname: Nicholas
  surname: Popescu
  middlename: C
  fullname: Popescu, Nicholas C
– sequence: 3
  givenname: Drazen
  surname: Zimonjic
  middlename: B
  fullname: Zimonjic, Drazen B
BookMark eNqNT8FKAzEUDEWhq-615weeYzfbbrderRYP0pM3kZKmbzXb5SWblwj69UYQz85lYGaY9-ZCnJEjFGKmqhul1qt5rW4XUq0rJReybiei-BOmomTuq4xVq5ZtVYjx_mmjgJP3AZmRYbeVLyftvX69A22i_bDxEyyBD46jjghGk8EABoeB4ZgQogMbGbJ7sIP9svQG2HVoIjgCfXzHgMTQJ8ptjvhKnHd6YCx_-VJcbx-eN48yXxgTctz3LgXK1j6Paeqm_nn_f6lv5hxRIQ
ContentType Journal Article
Copyright SpringerPlus is a copyright of Springer, 2014.
Copyright_xml – notice: SpringerPlus is a copyright of Springer, 2014.
DBID 3V.
7X2
8FE
8FG
8FH
8FK
ABJCF
AFKRA
ARAPS
ATCPS
AZQEC
BBNVY
BENPR
BGLVJ
BHPHI
BKSAR
CCPQU
D1I
DWQXO
GNUQQ
HCIFZ
JQ2
K7-
KB.
L6V
LK8
M0K
M7P
M7S
P5Z
P62
PATMY
PCBAR
PDBOC
PQEST
PQQKQ
PQUKI
PRINS
PTHSS
PYCSY
DOI 10.1186/2193-1801-3-27
DatabaseName ProQuest Central (Corporate)
Agricultural Science Collection
ProQuest SciTech Collection
ProQuest Technology Collection
ProQuest Natural Science Collection
ProQuest Central (Alumni) (purchase pre-March 2016)
Materials Science & Engineering Collection
ProQuest Central
Advanced Technologies & Aerospace Collection
Agricultural & Environmental Science Collection
ProQuest Central Essentials
Biological Science Collection
ProQuest Central
Technology Collection
Natural Science Collection
Earth, Atmospheric & Aquatic Science Collection
ProQuest One Community College
ProQuest Materials Science Collection
ProQuest Central Korea
ProQuest Central Student
SciTech Premium Collection
ProQuest Computer Science Collection
Computer Science Database
Materials Science Database
ProQuest Engineering Collection
Biological Sciences
Agriculture Science Database
Biological Science Database
Engineering Database
Advanced Technologies & Aerospace Database
ProQuest Advanced Technologies & Aerospace Collection
Environmental Science Database
Earth, Atmospheric & Aquatic Science Database
Materials Science Collection
ProQuest One Academic Eastern Edition (DO NOT USE)
ProQuest One Academic
ProQuest One Academic UKI Edition
ProQuest Central China
Engineering Collection
Environmental Science Collection
DatabaseTitle Agricultural Science Database
Computer Science Database
ProQuest Central Student
Technology Collection
ProQuest Advanced Technologies & Aerospace Collection
ProQuest Central Essentials
ProQuest Computer Science Collection
Materials Science Collection
SciTech Premium Collection
ProQuest One Community College
ProQuest Natural Science Collection
ProQuest Central China
Earth, Atmospheric & Aquatic Science Collection
ProQuest Central
ProQuest Engineering Collection
Natural Science Collection
ProQuest Central Korea
Agricultural & Environmental Science Collection
Biological Science Collection
Materials Science Database
Engineering Collection
ProQuest Materials Science Collection
Advanced Technologies & Aerospace Collection
Engineering Database
ProQuest Biological Science Collection
ProQuest One Academic Eastern Edition
Earth, Atmospheric & Aquatic Science Database
Agricultural Science Collection
ProQuest Technology Collection
Biological Science Database
ProQuest SciTech Collection
Environmental Science Collection
Advanced Technologies & Aerospace Database
ProQuest One Academic UKI Edition
Materials Science & Engineering Collection
Environmental Science Database
ProQuest One Academic
ProQuest Central (Alumni)
DatabaseTitleList Agricultural Science Database
Database_xml – sequence: 1
  dbid: 8FG
  name: ProQuest Technology Collection
  url: https://search.proquest.com/technologycollection1
  sourceTypes: Aggregation Database
DeliveryMethod fulltext_linktorsrc
Discipline Sciences (General)
EISSN 2193-1801
ExternalDocumentID 4312335131
GroupedDBID -A0
0R~
3V.
4.4
40G
53G
5VS
7X2
7XC
8CJ
8FE
8FG
8FH
8FK
AAKKN
AAYZJ
ABEEZ
ABJCF
ACACY
ACGFO
ACGFS
ACIWK
ACPRK
ACULB
ADBBV
ADINQ
ADRAZ
AEGXH
AENEX
AFGXO
AFKRA
AFRAH
AHBXF
AHBYD
AHSBF
AHYZX
AIAGR
ALMA_UNASSIGNED_HOLDINGS
AMKLP
AOIJS
ARAPS
ATCPS
AZQEC
BAWUL
BBNVY
BENPR
BGLVJ
BHPHI
BKSAR
C24
C6C
CCPQU
CZ9
D1I
D1J
D1K
DIK
DWQXO
EBS
EJD
GNUQQ
GROUPED_DOAJ
GX1
HCIFZ
HH5
HYE
HZ~
JQ2
K6-
K6V
K7-
KB.
KC.
KQ8
L6V
LK5
LK8
M0K
M48
M7P
M7R
M7S
M~E
O9-
OK1
P62
PATMY
PCBAR
PDBOC
PGMZT
PQEST
PQQKQ
PQUKI
PRINS
PTHSS
PYCSY
RNS
RPM
RSV
SHS
SOJ
ID FETCH-proquest_journals_18652522193
IEDL.DBID 8FG
IngestDate Thu Oct 10 19:30:57 EDT 2024
IsPeerReviewed true
IsScholarly true
Issue 1
Language English
LinkModel DirectLink
MergedId FETCHMERGED-proquest_journals_18652522193
PQID 1865252219
PQPubID 2034663
ParticipantIDs proquest_journals_1865252219
PublicationCentury 2000
PublicationDate 20140101
PublicationDateYYYYMMDD 2014-01-01
PublicationDate_xml – month: 01
  year: 2014
  text: 20140101
  day: 01
PublicationDecade 2010
PublicationPlace Heidelberg
PublicationPlace_xml – name: Heidelberg
PublicationTitle SpringerPlus
PublicationYear 2014
Publisher Springer Nature B.V
Publisher_xml – name: Springer Nature B.V
SSID ssj0000671470
Score 3.8173242
Snippet DLC1 (Deleted in Liver Cancer 1) gene encodes a RhoGTPase-activating protein (RhoGAP), which exerts most of its tumor suppressor functions through suppression...
SourceID proquest
SourceType Aggregation Database
StartPage 1
SummonAdditionalLinks – databaseName: Scholars Portal Open Access Journals
  dbid: M48
  link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwfV1LS8NAEB60XryI9YGPKgN60MNqHptkLyJaDUVsTxYKIiWPLbZKkuYB6q93NtniodLzsEt2JzPfN8s3uwDnwvRCQUBGtUk0YVwKzoRphmzCAxG6RAniUBWK_YHbG_KnkTP60z_pDSz-Le3Ue1LD_PPqa_59SwF_Uwe8cK8p6GxmUqplNrO8ddiwCBWVvKuvqb7Oyib3DH1v4_KwpVxcA4y_DVuaGeJd48o2rMlkB9o69gq80BdEX-7C_OG5a2JRZbWIlWwDn71-BFkWvN2jalRQ70HgNMFMtXQQmcRI-TZHdUpfYFxJLFOclgWSVYljfwi_sFF2YJpgEL-rJsACZwR69X-5B2f-40u3xxYfP15s4ZjW6FhEr2iZ-9BK0kQeALrSCYT0XGJegjsGZWrDDo04tomYxBGXh9BZNdPRavMxbBKh4M0RRQdaZV7JEwLtMjytvfEL3aKang
  priority: 102
  providerName: Scholars Portal
Title DLC1 suppresses NF-[kappa]B activity in prostate cancer cells due to its stabilizing effect on adherens junctions
URI https://www.proquest.com/docview/1865252219
Volume 3
hasFullText 1
inHoldings 1
isFullTextHit
isPrint
link http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwfV1NS8NAEB20vXgR6wd-1DKgBz0szTabZD2JrcYitogoFERKkt1iFZK0SS_-emfTrR6EHsOQJexs3rydfbMDcC55EEsKZLQ3SSZMaCmY5DxmExHJ2CdKoGKzURwM_f6reBh5I5twK6yscoWJFVCrLDE58jaXvtchssCvrvMZM12jzOmqbaGxCXXeCXwj6ZPh_W-OhZCYi8CxdzXSCG163WWcUJm5rBP8w98qqIQ7sG3ZIN4s3deADZ3uQsP-bwVe2EuhL_dgdvvY41gs8kq4SrZhyN6-ojyP3rtoihNMDwicppibMg4ikJgYf87RZOYLVAuNZYbTskCyGkHsN8UsXKo5MEsxUh-m8K_ATwp01Vrch7Pw7qXXZ6uPH9t1V4z_Zsk9gFqapfoQ0NdeJHXgE9uSwnMInR03dpRyiYyoROgjaK4b6Xi9-QS2iESIZVqiCbVyvtCnFKjLuFV5owX17t3w6ZmeBkL-AOssmvE
link.rule.ids 314,780,784,12765,21388,24318,27924,27925,33373,33744,43600,43805
linkProvider ProQuest
linkToHtml http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwfV07T8MwED5BGWBBlId4FDgJBhisxo2TmAnxCgXaTkWqhFCVxK4oSEnapAu_nnPqwoDU-WQrytnf9_l85wM4lzyIJREZnU2SERNaCiY5j9lIRDL2SRKo2BwUuz2__SqeB97ABtwKm1a5wMQKqFWWmBh5k0vfa5FY4FfX-YSZrlHmdtW20FiFNeESdZtK8fDxN8ZCSMxF4Ni3GmmGJg13GSdUZi5rBf_wtyKVcAs2rRrEm7n76rCi022o2_1W4IV9FPpyByb3nTuOxSyvElfJ1gvZ21eU59H7LZriBNMDAscp5qaMgwQkJsafUzSR-QLVTGOZ4bgskKwmIfabOAvn2RyYpRipD1P4V-AnEV21FnfhLHzo37XZ4uOHdt0Vw7-_5O5BLc1SvQ_oay-SOvBJbUnhOYTOjhs7SrkkRlQi9AE0ls10uNx8Cuvtfrcz7Dz1Xo5ggwSFmIcoGlArpzN9TKRdxieVZ34AvjGbXw
openUrl ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=DLC1+suppresses+NF-%5Bkappa%5DB+activity+in+prostate+cancer+cells+due+to+its+stabilizing+effect+on+adherens+junctions&rft.jtitle=SpringerPlus&rft.au=Tripathi%2C+Veenu&rft.au=Popescu%2C+Nicholas+C&rft.au=Zimonjic%2C+Drazen+B&rft.date=2014-01-01&rft.pub=Springer+Nature+B.V&rft.eissn=2193-1801&rft.volume=3&rft.issue=1&rft.spage=1&rft_id=info:doi/10.1186%2F2193-1801-3-27&rft.externalDocID=4312335131