Evidence map›Paper›PMID 27955654›Full record

ArticleMolecular cancer2016

Depletion of SAG/RBX2 E3 ubiquitin ligase suppresses prostate tumorigenesis via inactivation of the PI3K/AKT/mTOR axis.

Mingjia Tan, Jie Xu, Javed Siddiqui, Felix Feng, Yi Sun

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular cancer, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
1.6field-weighted citation impact, top 16% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

32 citing papers in PubMed, 50 citations in OpenAlex.

  1. Review
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  4. FBXO22 inhibits colitis and colorectal carcinogenesis by regulating the degradation of the S2448-phosphorylated form of mTOR.Proceedings of the National Academy of Sciences of the United States of America · 2024
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  16. The roles of KLHL family members in human cancers.American journal of cancer research · 2022
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 3 institutions in 2 countries.

Mingjia TanDivision of Radiation and Cancer Biology, Department of Radiation Oncology, 4424B MS-1, 1301 Catherine Street, Ann Arbor, 48109, MI, USA.
Jie XuDivision of Radiation and Cancer Biology, Department of Radiation Oncology, 4424B MS-1, 1301 Catherine Street, Ann Arbor, 48109, MI, USA.
Javed SiddiquiDepartment of Pathology, University of Michigan, 4424B MS-1, 1301 Catherine Street, Ann Arbor, 48109, MI, USA.
Felix FengDivision of Radiation and Cancer Biology, Department of Radiation Oncology, 4424B MS-1, 1301 Catherine Street, Ann Arbor, 48109, MI, USA.
Yi SunDivision of Radiation and Cancer Biology, Department of Radiation Oncology, 4424B MS-1, 1301 Catherine Street, Ann Arbor, 48109, MI, USA. sunyi@umich.edu.
University of Michigan–Ann Arbor · USUniversity of San Francisco · USZhejiang University · CN

Funding

The role of FBXW2 as a novel lung tumor suppressor that cross-talks with oncogenic beta-TrCP and SKP2R01CA156744 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MORGAN, MEREDITH A · 2011 to 2020
$3.4M
SAG E3 ubiquitin ligase in regulation of transformation and carcinogenesisR01CA118762 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI SUN, YI · 2006 to 2015
$2.6M
Role of SAG/RBX2 E3 Ubiquitin Ligase in Skin CarcinogenesisR01CA171277 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI SUN, YI · 2013 to 2017
$1.6M
NCI NIH HHS R01 CA118762NCI NIH HHS R01 CA156744NCI NIH HHS R01 CA171277
6 · The paper itself

Abstract

backgroundSAG (Sensitive to Apoptosis Gene), also known as RBX2, ROC2 or RNF7, is a RING component of CRL (Cullin-RING ligase), required for its activity. Our recent study showed that SAG/RBX2 co-operated with Kras to promote lung tumorigenesis, but antagonized Kras to inhibit skin tumorigenesis, suggesting a tissue/context dependent function of Sag. However, it is totally unknown whether and how Sag would play in prostate tumorigenesis, triggered by Pten loss.

methodsSag and Pten double conditional knockout mice were generated and prostate specific deletion of Sag and Pten was achieved by PB4-Cre, and their effect on prostate tumorigenesis was evaluated by H&E staining. The methods of immunohistochemistry (IHC) staining and Western blotting were utilized to examine expression of various proteins in prostate cancer tissues or cell lines. The effect of SAG knockdown in proliferation, survival and migration was evaluated in two prostate cancer cell lines. The poly-ubiquitylation of PHLPP1 and DEPTOR was evaluated by both in vivo and in vitro ubiquitylation assays.

resultsSAG is overexpressed progressively from early-to-late stage of human prostate cancer with the highest expression seen in metastatic lesion. Sag deletion inhibits prostate tumorigenesis triggered by Pten loss in a mouse model as a result of suppressed proliferation. SAG knockdown in human prostate cancer cells inhibits a) proliferation in monolayer and soft agar, b) clonogenic survival, and c) migration. SAG is an E3 ligase that promotes ubiquitylation and degradation of PHLPP1 and DEPTOR, leading to activation of the PI3K/AKT/mTOR axis, whereas SAG knockdown caused their accumulation. Importantly, growth suppression triggered by SAG knockdown was partially rescued by simultaneous knockdown of PHLPP1 or DEPTOR, suggesting their causal role. Accumulation of Phlpp1 and Deptor with corresponding inactivation of Akt/mTOR was also detected in Sag-null prostate cancer tissues.

conclusionsSag is an oncogenic cooperator of Pten-loss for prostate tumorigenesis. Targeting SAG E3 ligase may, therefore, have therapeutic value for the treatment of prostate cancer associated with Pten loss.

Indexed as

AnimalsApoptosisCarrier ProteinsCell Line, TumorCell MovementCell ProliferationHumansMaleMiceMice, KnockoutPhosphatidylinositol 3-KinasesProstatic NeoplasmsProto-Oncogene Proteins c-aktPTEN PhosphohydrolaseSignal TransductionTOR Serine-Threonine KinasesCarrier ProteinsmTOR protein, mousePhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktPTEN PhosphohydrolasePten protein, mouseSAG protein, mouseTOR Serine-Threonine KinasesDEPTORPHLPP1Prostate tumorigenesisPtenSAG KOSAG-SCF E3Ubiquitin ligase

Identifiers

PMID27955654
PMCPMC5153812
OpenAlexW2565348573

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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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 OpenQuestion graph.