PMID- 33077835
OWN - NLM
STAT- MEDLINE
DCOM- 20201211
LR  - 20220421
IS  - 1476-5594 (Electronic)
IS  - 0950-9232 (Linking)
VI  - 39
IP  - 46
DP  - 2020 Nov
TI  - Tenascin C promotes cancer cell plasticity in mesenchymal glioblastoma.
PG  - 6990-7004
LID - 10.1038/s41388-020-01506-6 [doi]
AB  - Interconversion of transformed non-stem cells to cancer stem cells, termed cancer 
      cell plasticity, contributes to intra-tumor heterogeneity and its molecular 
      mechanisms are currently unknown. Here, we have identified Tenascin C (TNC) to be 
      upregulated and secreted in mesenchymal glioblastoma (MES GBM) subtype with high 
      NF-kappaB signaling activity. Silencing TNC decreases proliferation, migration and 
      suppresses self-renewal of glioma stem cells. Loss of TNC in MES GBM compromises 
      de-differentiation of transformed astrocytes and blocks the ability of glioma 
      stem cells to differentiate into tumor derived endothelial cells (TDEC). 
      Inhibition of NF-kappaB activity or TNC knockdown in tumor cells decreased their 
      tumorigenic potential in vivo. Our results uncover a link between NF-kappaB 
      activation in MES GBM and high levels of TNC in GBM extracellular matrix. We 
      suggest that TNC plays an important role in the autocrine regulation of glioma 
      cell plasticity and hence can be a potential molecular target for MES GBM.
FAU - Angel, Inbar
AU  - Angel I
AD  - School of Neurobiology, Biochemistry and Biophysics, The George S. Wise Faculty 
      of Life Sciences, Tel Aviv University, Tel Aviv-Yafo, Israel.
FAU - Pilo Kerman, Ori
AU  - Pilo Kerman O
AD  - School of Neurobiology, Biochemistry and Biophysics, The George S. Wise Faculty 
      of Life Sciences, Tel Aviv University, Tel Aviv-Yafo, Israel.
FAU - Rousso-Noori, Liat
AU  - Rousso-Noori L
AD  - School of Neurobiology, Biochemistry and Biophysics, The George S. Wise Faculty 
      of Life Sciences, Tel Aviv University, Tel Aviv-Yafo, Israel.
FAU - Friedmann-Morvinski, Dinorah
AU  - Friedmann-Morvinski D
AUID- ORCID: 0000-0002-6394-9876
AD  - School of Neurobiology, Biochemistry and Biophysics, The George S. Wise Faculty 
      of Life Sciences, Tel Aviv University, Tel Aviv-Yafo, Israel. 
      dino@tauex.tau.ac.il.
AD  - Sagol School of Neuroscience, Tel Aviv University, Tel Aviv-Yafo, Israel. 
      dino@tauex.tau.ac.il.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20201019
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (NF-kappa B)
RN  - 0 (TNC protein, human)
RN  - 0 (Tenascin)
SB  - IM
MH  - Animals
MH  - Astrocytes/pathology
MH  - Brain Neoplasms/*pathology
MH  - Cell Dedifferentiation
MH  - Cell Plasticity
MH  - Cell Transformation, Neoplastic/pathology
MH  - Extracellular Matrix/pathology
MH  - Female
MH  - Gene Knockdown Techniques
MH  - Glioblastoma/*pathology
MH  - Humans
MH  - Mesenchymal Stem Cells/*pathology
MH  - Mice
MH  - Mice, Transgenic
MH  - NF-kappa B/metabolism
MH  - Neoplastic Stem Cells/*pathology
MH  - Tenascin/genetics/*metabolism
MH  - Tumor Microenvironment
MH  - Xenograft Model Antitumor Assays
EDAT- 2020/10/21 06:00
MHDA- 2020/12/15 06:00
CRDT- 2020/10/20 06:20
PHST- 2020/01/06 00:00 [received]
PHST- 2020/10/01 00:00 [accepted]
PHST- 2020/09/17 00:00 [revised]
PHST- 2020/10/21 06:00 [pubmed]
PHST- 2020/12/15 06:00 [medline]
PHST- 2020/10/20 06:20 [entrez]
AID - 10.1038/s41388-020-01506-6 [pii]
AID - 10.1038/s41388-020-01506-6 [doi]
PST - ppublish
SO  - Oncogene. 2020 Nov;39(46):6990-7004. doi: 10.1038/s41388-020-01506-6. Epub 2020 
      Oct 19.