PMID- 36878305
OWN - NLM
STAT- MEDLINE
DCOM- 20230523
LR  - 20230523
IS  - 1879-260X (Electronic)
IS  - 0925-4439 (Linking)
VI  - 1869
IP  - 5
DP  - 2023 Jun
TI  - Tenascin-C affects invasiveness of EGFR-mutated lung adenocarcinoma through a 
      putative paracrine loop.
PG  - 166684
LID - S0925-4439(23)00050-9 [pii]
LID - 10.1016/j.bbadis.2023.166684 [doi]
AB  - Tenascin C (TNC) is an extracellular matrix (ECM) protein and a potential 
      biomarker affecting progression of different tumor types, such as pancreatic and 
      lung cancer. Alternative splicing variants of TNC are known to have an impact on 
      interaction partners like other ECM proteins or cell surface receptors, including 
      epidermal growth factor receptor (EGFR), leading to numerous and sometimes 
      opposite roles of TNC in tumor cell dissemination and proliferation. Only little 
      is known about the impact of TNC on biologic characteristics of lung cancer, such 
      as invasion and metastatic potential. In the present study, we could link an 
      increased expression of TNC in lung adenocarcinoma (LUAD) tissues with an 
      unfavorable clinical outcome of patients. Furthermore, we investigated the 
      functional role of TNC in LUAD. Immunohistochemical staining of TNC revealed a 
      significant increase of TNC levels in primary tumours and metastases compared to 
      normal lung tissue. Additionally, a significant correlation between TNC mRNA 
      expression and EGFR copy number and protein expression levels has been 
      determined. Moreover, inhibition of TNC in lung fibroblasts led to reduced 
      invasiveness of LUAD cells harboring EGFR-activating mutations and to a shorter 
      lamellipodia perimeter and a reduced lamellipodia area on the surface of LUAD 
      cells. This study provides the evidence that TNC expression might be a biological 
      relevant factor in LUAD progression in an EGFR-dependent manner and that it 
      regulates tumor cell invasion by rearrangement of the actin cytoskeleton, 
      especially affecting lamellipodia formation.
CI  - Copyright (c) 2023 Elsevier B.V. All rights reserved.
FAU - Schlensog, Martin
AU  - Schlensog M
AD  - Institute of Pathology, Medical Faculty of the Heinrich Heine University, 
      Duesseldorf, Germany.
FAU - Ruehlmann, Ann-Cathrin
AU  - Ruehlmann AC
AD  - Institute of Pathology, Medical Faculty of the Heinrich Heine University, 
      Duesseldorf, Germany.
FAU - Haeberle, Lena
AU  - Haeberle L
AD  - Institute of Pathology, Medical Faculty of the Heinrich Heine University, 
      Duesseldorf, Germany.
FAU - Opitz, Friederike
AU  - Opitz F
AD  - Institute of Pathology, Medical Faculty of the Heinrich Heine University, 
      Duesseldorf, Germany.
FAU - Becher, Ann-Kathrin
AU  - Becher AK
AD  - Institute of Pathology, Medical Faculty of the Heinrich Heine University, 
      Duesseldorf, Germany.
FAU - Goering, Wolfgang
AU  - Goering W
AD  - Institute of Pathology, Medical Faculty of the Heinrich Heine University, 
      Duesseldorf, Germany.
FAU - Buth, Juliane
AU  - Buth J
AD  - Institute of Pathology, Medical Faculty of the Heinrich Heine University, 
      Duesseldorf, Germany.
FAU - Knoefel, Wolfram Trudo
AU  - Knoefel WT
AD  - Department of General, Visceral and Pediatric Surgery, Medical Faculty of the 
      Heinrich Heine University, Duesseldorf, Germany.
FAU - Ladage, Dennis
AU  - Ladage D
AD  - Department of Pneumology, Kliniken Maria Hilf GmbH, Moenchengladbach, Germany.
FAU - Meyer, Andreas
AU  - Meyer A
AD  - Department of Pneumology, Kliniken Maria Hilf GmbH, Moenchengladbach, Germany.
FAU - Esposito, Irene
AU  - Esposito I
AD  - Institute of Pathology, Medical Faculty of the Heinrich Heine University, 
      Duesseldorf, Germany. Electronic address: irene.esposito@med.uni-duesseldorf.de.
LA  - eng
PT  - Journal Article
DEP - 20230304
PL  - Netherlands
TA  - Biochim Biophys Acta Mol Basis Dis
JT  - Biochimica et biophysica acta. Molecular basis of disease
JID - 101731730
RN  - EC 2.7.10.1 (EGFR protein, human)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - 0 (Tenascin)
RN  - 0 (TNC protein, human)
SB  - IM
MH  - Humans
MH  - *Adenocarcinoma of Lung/genetics/metabolism
MH  - ErbB Receptors/genetics/metabolism
MH  - Extracellular Matrix/metabolism
MH  - *Lung Neoplasms/genetics/metabolism
MH  - Tenascin/genetics/metabolism
OTO - NOTNLM
OT  - EGFR
OT  - LUAD
OT  - Lung cancer
OT  - TNC
OT  - cancer invasion
COIS- Declaration of competing interest The authors declare no potential conflicts of 
      interest for the following manuscript.
EDAT- 2023/03/07 06:00
MHDA- 2023/05/08 10:17
CRDT- 2023/03/06 19:23
PHST- 2022/09/12 00:00 [received]
PHST- 2023/01/26 00:00 [revised]
PHST- 2023/02/28 00:00 [accepted]
PHST- 2023/05/08 10:17 [medline]
PHST- 2023/03/07 06:00 [pubmed]
PHST- 2023/03/06 19:23 [entrez]
AID - S0925-4439(23)00050-9 [pii]
AID - 10.1016/j.bbadis.2023.166684 [doi]
PST - ppublish
SO  - Biochim Biophys Acta Mol Basis Dis. 2023 Jun;1869(5):166684. doi: 
      10.1016/j.bbadis.2023.166684. Epub 2023 Mar 4.