TIS21/BTG2 inhibits breast cancer growth and progression by differential regulation of mTORc1 and mTORc2–AKT1–NFAT1–PHLPP2 signaling axis

TIS21/BTG2 inhibits breast cancer growth and progression by differential regulation of mTORc1 and... Purpose It has been reported that PI3K/AKT pathway is altered in various cancers and AKT isoforms specifically regulate cell growth and metastasis of cancer cells; AKT1, but not AKT2, reduces invasion of cancer cells but maintains cancer /BTG2 growth. We propose here a novel mechanism of the tumor suppresser, TIS21 , that inhibits both growth and invasion of triple negative breast cancer cells via AKT1 activation by differential regulation of mTORc1 and mTORc2 activity. /BTG2 Methods Transduction of adenovirus carrying TIS21 gene and transfection of short interfering RNAs were employed /BTG2 to regulate TIS21 gene expression in various cell lines. Treatment of mTOR inhibitors and mTOR kinase assays can /BTG2 evaluate the role of mTORc in the regulation of AKT phosphorylation at S473 residue by TIS21 in breast cancer cells. /BTG2 Open data and immunohistochemical analysis were performed to confirm the role of TIS21 expression in various human breast cancer tissues. /BTG2 Results We observed that TIS21 inhibited mTORc1 activity by reducing Raptor-mTOR interaction along with upregu- S473 lation of tsc1 expression, which lead to significant reduction of p70S6K activation as opposed to AKT1 , but not AKT2, /BTG2 S473 phosphorylation via downregulating PHLPP2 (AKT1-specific phosphatase) in breast cancers. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Cancer Research and Clinical Oncology Springer Journals

TIS21/BTG2 inhibits breast cancer growth and progression by differential regulation of mTORc1 and mTORc2–AKT1–NFAT1–PHLPP2 signaling axis

Loading next page...
 
/lp/springer_journal/tis21-btg2-inhibits-breast-cancer-growth-and-progression-by-ILYRk0IPEt
Publisher
Springer Journals
Copyright
Copyright © 2018 by Springer-Verlag GmbH Germany, part of Springer Nature
Subject
Medicine & Public Health; Oncology; Cancer Research; Internal Medicine; Hematology
ISSN
0171-5216
eISSN
1432-1335
D.O.I.
10.1007/s00432-018-2677-6
Publisher site
See Article on Publisher Site

Abstract

Purpose It has been reported that PI3K/AKT pathway is altered in various cancers and AKT isoforms specifically regulate cell growth and metastasis of cancer cells; AKT1, but not AKT2, reduces invasion of cancer cells but maintains cancer /BTG2 growth. We propose here a novel mechanism of the tumor suppresser, TIS21 , that inhibits both growth and invasion of triple negative breast cancer cells via AKT1 activation by differential regulation of mTORc1 and mTORc2 activity. /BTG2 Methods Transduction of adenovirus carrying TIS21 gene and transfection of short interfering RNAs were employed /BTG2 to regulate TIS21 gene expression in various cell lines. Treatment of mTOR inhibitors and mTOR kinase assays can /BTG2 evaluate the role of mTORc in the regulation of AKT phosphorylation at S473 residue by TIS21 in breast cancer cells. /BTG2 Open data and immunohistochemical analysis were performed to confirm the role of TIS21 expression in various human breast cancer tissues. /BTG2 Results We observed that TIS21 inhibited mTORc1 activity by reducing Raptor-mTOR interaction along with upregu- S473 lation of tsc1 expression, which lead to significant reduction of p70S6K activation as opposed to AKT1 , but not AKT2, /BTG2 S473 phosphorylation via downregulating PHLPP2 (AKT1-specific phosphatase) in breast cancers.

Journal

Journal of Cancer Research and Clinical OncologySpringer Journals

Published: May 28, 2018

References

You’re reading a free preview. Subscribe to read the entire article.


DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Search

Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly

Organize

Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.

Access

Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

DeepDyve

Freelancer

DeepDyve

Pro

Price

FREE

$49/month
$360/year

Save searches from
Google Scholar,
PubMed

Create lists to
organize your research

Export lists, citations

Read DeepDyve articles

Abstract access only

Unlimited access to over
18 million full-text articles

Print

20 pages / month

PDF Discount

20% off