PMID- 31717665
OWN - NLM
STAT- MEDLINE
DCOM- 20200413
LR  - 20200413
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 20
IP  - 22
DP  - 2019 Nov 10
TI  - Transcription Factor Prospero Homeobox 1 (PROX1) as a Potential Angiogenic 
      Regulator of Follicular Thyroid Cancer Dissemination.
LID - 10.3390/ijms20225619 [doi]
LID - 5619
AB  - It is well known that Prospero homeobox 1 (PROX1) is a crucial regulator of 
      lymphangiogenesis, that reprograms blood endothelial cells to lymphatic 
      phenotype. However, the role of PROX1 in tumor progression, especially in 
      angiogenesis remains controversial. Herein, we studied the role of PROX1 in 
      angiogenesis in cell lines derived from follicular thyroid cancer (FTC: FTC-133) 
      and squamous cell carcinoma of the thyroid gland (SCT: CGTH-W-1) upon PROX1 
      knockdown. The genes involved in angiogenesis were selected by RNA-seq, and the 
      impact of PROX1 on vascularization potential was investigated using human 
      umbilical vein endothelial cells (HUVECs) cultured in conditioned medium 
      collected from FTC- or SCT-derived cancer cell lines after PROX1 silencing. The 
      angiogenic phenotype was examined in connection with the analysis of focal 
      adhesion and correlated with fibroblast growth factor 2 (FGF2) levels. 
      Additionally, the expression of selected genes involved in angiogenesis was 
      detected in human FTC tissues. As a result, we demonstrated that PROX1 knockdown 
      resulted in upregulation of factors associated with vascularization, such as 
      metalloproteinases (MMP1 and 3), FGF2, vascular endothelial growth factors C 
      (VEGFC), BAI1 associated protein 2 (BAIAP2), nudix hydrolase 6 (NUDT6), 
      angiopoietin 1 (ANGPT1), and vascular endothelial growth factor receptor 2 (KDR). 
      The observed molecular changes resulted in the enhanced formation of 
      capillary-like structures by HUVECs and upregulated focal adhesion in FTC-133 and 
      CGTH-W-1 cells. The signature of selected angiogenic genes' expression in a 
      series of FTC specimens varied depending on the case. Interestingly, PROX1 and 
      FGF2 showed opposing expression levels in FTC tissues and seven thyroid 
      tumor-derived cell lines. In summary, our data revealed that PROX1 is involved in 
      the spreading of thyroid cancer cells by regulation of angiogenesis.
FAU - Rudzinska, Magdalena
AU  - Rudzinska M
AD  - Centre of Postgraduate Medical Education, Department of Biochemistry and 
      Molecular Biology, 01-813 Warsaw, Poland.
AD  - Institute of Molecular Medicine, Sechenov First Moscow State Medical University, 
      119991 Moscow, Russia.
FAU - Mikula, Michal
AU  - Mikula M
AD  - Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, 
      Department of Genetics, 02-781 Warsaw, Poland.
FAU - Arczewska, Katarzyna D
AU  - Arczewska KD
AUID- ORCID: 0000-0001-9606-1585
AD  - Centre of Postgraduate Medical Education, Department of Biochemistry and 
      Molecular Biology, 01-813 Warsaw, Poland.
FAU - Gajda, Ewa
AU  - Gajda E
AUID- ORCID: 0000-0002-3774-3989
AD  - Centre of Postgraduate Medical Education, Department of Biochemistry and 
      Molecular Biology, 01-813 Warsaw, Poland.
FAU - Sabalinska, Stanislawa
AU  - Sabalinska S
AD  - Nalecz Institute of Biocybernetics and Biomedical Engineering, Polish Academy of 
      Sciences, 02-109 Warsaw, Poland.
FAU - Stepien, Tomasz
AU  - Stepien T
AD  - Clinic of Endocrinological and General Surgery, Medical University of Lodz, 
      91-513 Lodz, Poland.
FAU - Ostrowski, Jerzy
AU  - Ostrowski J
AD  - Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, 
      Department of Genetics, 02-781 Warsaw, Poland.
AD  - Centre of Postgraduate Medical Education, Department of Gastroenterology, 
      Hepatology and Clinical Oncology, 02-781 Warsaw, Poland.
FAU - Czarnocka, Barbara
AU  - Czarnocka B
AUID- ORCID: 0000-0001-7701-760X
AD  - Centre of Postgraduate Medical Education, Department of Biochemistry and 
      Molecular Biology, 01-813 Warsaw, Poland.
LA  - eng
GR  - 2013/11/N/NZ5/03394/Narodowe Centrum Nauki/
GR  - 2012/07/B/ NZ5/02444/Narodowe Centrum Nauki/
PT  - Journal Article
DEP - 20191110
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Endothelial Growth Factors)
RN  - 0 (Homeodomain Proteins)
RN  - 0 (Tumor Suppressor Proteins)
RN  - 0 (prospero-related homeobox 1 protein)
RN  - Thyroid cancer, follicular
SB  - IM
MH  - Adenocarcinoma, Follicular/blood supply/metabolism/*pathology
MH  - Carcinoma, Squamous Cell/blood supply/metabolism/*pathology
MH  - Cells, Cultured
MH  - Endothelial Growth Factors/genetics/metabolism
MH  - *Gene Expression Regulation, Neoplastic
MH  - Homeodomain Proteins/antagonists & inhibitors/genetics/*metabolism
MH  - Humans
MH  - Neovascularization, Pathologic/metabolism/*pathology
MH  - Thyroid Gland/metabolism/*pathology
MH  - Thyroid Neoplasms/blood supply/metabolism/*pathology
MH  - Tumor Suppressor Proteins/antagonists & inhibitors/genetics/*metabolism
PMC - PMC6888435
OTO - NOTNLM
OT  - PROX1
OT  - angiogenesis
OT  - follicular thyroid cancer
COIS- The authors declare no conflict of interest. The authors alone are responsible 
      for the content and writing of the paper.
EDAT- 2019/11/14 06:00
MHDA- 2020/04/14 06:00
PMCR- 2019/11/01
CRDT- 2019/11/14 06:00
PHST- 2019/10/08 00:00 [received]
PHST- 2019/11/06 00:00 [revised]
PHST- 2019/11/07 00:00 [accepted]
PHST- 2019/11/14 06:00 [entrez]
PHST- 2019/11/14 06:00 [pubmed]
PHST- 2020/04/14 06:00 [medline]
PHST- 2019/11/01 00:00 [pmc-release]
AID - ijms20225619 [pii]
AID - ijms-20-05619 [pii]
AID - 10.3390/ijms20225619 [doi]
PST - epublish
SO  - Int J Mol Sci. 2019 Nov 10;20(22):5619. doi: 10.3390/ijms20225619.