PMID- 34633031
OWN - NLM
STAT- MEDLINE
DCOM- 20211203
LR  - 20220531
IS  - 1477-9137 (Electronic)
IS  - 0021-9533 (Linking)
VI  - 134
IP  - 21
DP  - 2021 Nov 1
TI  - The long non-coding RNA ET-20 mediates EMT by impairing desmosomes in breast 
      cancer cells.
LID - jcs258418 [pii]
LID - 10.1242/jcs.258418 [doi]
AB  - The vast majority of breast cancer-associated deaths are due to metastatic spread 
      of cancer cells, a process aided by epithelial-to-mesenchymal transition (EMT). 
      Mounting evidence has indicated that long non-coding RNAs (lncRNAs) also 
      contribute to tumor progression. We report the identification of 114 novel 
      lncRNAs that change their expression during TGFbeta-induced EMT in murine breast 
      cancer cells (referred to as EMT-associated transcripts; ETs). Of these, the 
      ET-20 gene localizes in antisense orientation within the tenascin C (Tnc) gene 
      locus. TNC is an extracellular matrix protein that is critical for EMT and 
      metastasis formation. Both ET-20 and Tnc are regulated by the EMT master 
      transcription factor Sox4. Notably, ablation of ET-20 lncRNA effectively blocks 
      Tnc expression and with it EMT. Mechanistically, ET-20 interacts with desmosomal 
      proteins, thereby impairing epithelial desmosomes and promoting EMT. A short 
      transcript variant of ET-20 is shown to be upregulated in invasive human breast 
      cancer cell lines, where it also promotes EMT. Targeting ET-20 appears to be a 
      therapeutically attractive lead to restrain EMT and breast cancer metastasis in 
      addition to its potential utility as a biomarker for invasive breast cancer.
CI  - (c) 2021. Published by The Company of Biologists Ltd.
FAU - Saxena, Meera
AU  - Saxena M
AUID- ORCID: 0000-0002-4060-4218
AD  - Department of Biomedicine, University of Basel, 4058 Basel, Switzerland.
FAU - Hisano, Mizue
AU  - Hisano M
AD  - Department of Biomedicine, University of Basel, 4058 Basel, Switzerland.
FAU - Neutzner, Melanie
AU  - Neutzner M
AD  - Department of Biomedicine, University of Basel, 4058 Basel, Switzerland.
FAU - Diepenbruck, Maren
AU  - Diepenbruck M
AD  - Department of Biomedicine, University of Basel, 4058 Basel, Switzerland.
FAU - Ivanek, Robert
AU  - Ivanek R
AD  - Department of Biomedicine, University of Basel, 4058 Basel, Switzerland.
AD  - Swiss Institute of Bioinformatics, 4058 Basel, Switzerland.
FAU - Sharma, Kirti
AU  - Sharma K
AUID- ORCID: 0000-0003-3704-1466
AD  - Proteomics Kymera Therapeutics Basel Cambridge, MA 02472, USA.
FAU - Kalathur, Ravi K R
AU  - Kalathur RKR
AUID- ORCID: 0000-0003-2894-3345
AD  - Department of Biomedicine, University of Basel, 4058 Basel, Switzerland.
AD  - Murdoch Children's Research Institute, Royal Children's Hospital, 3052 Parkville, 
      Australia.
FAU - Burglin, Thomas R
AU  - Burglin TR
AD  - Department of Biomedicine, University of Basel, 4058 Basel, Switzerland.
FAU - Risoli, Salvatore
AU  - Risoli S
AUID- ORCID: 0000-0001-9125-1435
AD  - Department of Biomedicine, University of Basel, 4058 Basel, Switzerland.
FAU - Christofori, Gerhard
AU  - Christofori G
AUID- ORCID: 0000-0002-8696-9896
AD  - Department of Biomedicine, University of Basel, 4058 Basel, Switzerland.
LA  - eng
GR  - MetastasiX (2014/268)/SNSF_/Swiss National Science Foundation/Switzerland
GR  - 310030B_163471/SNSF_/Swiss National Science Foundation/Switzerland
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20211105
PL  - England
TA  - J Cell Sci
JT  - Journal of cell science
JID - 0052457
RN  - 0 (RNA, Long Noncoding)
RN  - 0 (SOX4 protein, human)
RN  - 0 (SOXC Transcription Factors)
SB  - IM
MH  - Animals
MH  - *Breast Neoplasms/genetics
MH  - Cell Line, Tumor
MH  - Desmosomes/genetics
MH  - Epithelial-Mesenchymal Transition/genetics
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Mice
MH  - Neoplasm Invasiveness/genetics
MH  - *RNA, Long Noncoding/genetics
MH  - SOXC Transcription Factors
OTO - NOTNLM
OT  - Breast cancer
OT  - Desmosomes
OT  - EMT
OT  - Metastasis
OT  - Tenascin C
OT  - lncRNA
COIS- Competing interests The authors declare no competing or financial interests.
EDAT- 2021/10/12 06:00
MHDA- 2021/12/15 06:00
CRDT- 2021/10/11 08:53
PHST- 2021/01/23 00:00 [received]
PHST- 2021/09/24 00:00 [accepted]
PHST- 2021/10/12 06:00 [pubmed]
PHST- 2021/12/15 06:00 [medline]
PHST- 2021/10/11 08:53 [entrez]
AID - 272428 [pii]
AID - 10.1242/jcs.258418 [doi]
PST - ppublish
SO  - J Cell Sci. 2021 Nov 1;134(21):jcs258418. doi: 10.1242/jcs.258418. Epub 2021 Nov 
      5.