PMID- 37518985
OWN - NLM
STAT- MEDLINE
DCOM- 20231006
LR  - 20231013
IS  - 1878-0261 (Electronic)
IS  - 1574-7891 (Print)
IS  - 1574-7891 (Linking)
VI  - 17
IP  - 10
DP  - 2023 Oct
TI  - Promyelocytic leukemia protein regulates angiogenesis and epithelial-mesenchymal 
      transition to limit metastasis in MDA-MB-231 breast cancer cells.
PG  - 2090-2108
LID - 10.1002/1878-0261.13501 [doi]
AB  - Promyelocytic leukemia protein (PML) modulates diverse cell functions that 
      contribute to both tumor suppressor and pro-oncogenic effects, depending on the 
      cellular context. We show here that PML knockdown (KD) in MDA-MB-231, but not 
      MCF7, breast cancer cells, prolonged stem-cell-like survival, and increased cell 
      proliferation and migration, which is in line with gene-enrichment results from 
      their RNA sequencing analysis. Of note, increased migration was accompanied by 
      higher levels of the epithelial-mesenchymal transition (EMT) regulator 
      Twist-related protein 2 (TWIST2). We showed here that PML binds to TWIST2 via its 
      basic helix-loop-helix (bHLH) region and functionally interferes with the 
      suppression of the epithelial target of TWIST2, CD24. In addition, PML ablation 
      in MDA-MB-231 cells led to higher protein levels of hypoxia-inducible factor 
      1-alpha (HIF1a), resulting in a higher cell hypoxic response. Functionally, PML 
      directly suppressed the induction of the HIF1a target gene vascular endothelial 
      growth factor A (VEGFa). In line with these results, tumor xenografts of 
      MDA-MB-231 PML-KD cells had enhanced aggressive properties, including higher 
      microvessel density, faster local growth, and higher metastatic ability, with a 
      preference for lung. Collectively, PML suppresses the cancer aggressive behavior 
      by multiple mechanisms that impede both the HIF-hypoxia-angiogenic and EMT 
      pathways.
CI  - (c) 2023 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on 
      behalf of Federation of European Biochemical Societies.
FAU - Vogiatzoglou, Amalia P
AU  - Vogiatzoglou AP
AUID- ORCID: 0000-0002-6187-1075
AD  - Institute of Molecular Biology and Biotechnology (IMBB), Foundation for Research 
      and Technology-Hellas (FORTH), Crete, Greece.
AD  - Department of Biology, University of Crete, Heraklion, Greece.
FAU - Spanou, Syrago
AU  - Spanou S
AD  - Institute of Molecular Biology and Biotechnology (IMBB), Foundation for Research 
      and Technology-Hellas (FORTH), Crete, Greece.
AD  - Department of Biology, University of Crete, Heraklion, Greece.
FAU - Sachini, Nikoleta
AU  - Sachini N
AD  - Institute of Molecular Biology and Biotechnology (IMBB), Foundation for Research 
      and Technology-Hellas (FORTH), Crete, Greece.
AD  - Department of Biology, University of Crete, Heraklion, Greece.
AD  - ADC Therapeutics Limited, London, UK.
FAU - Drakos, Elias
AU  - Drakos E
AD  - Department of Pathology, Medical School, University of Crete, Greece.
FAU - Nikolaou, Christoforos
AU  - Nikolaou C
AD  - Biomedical Sciences Research Center "Alexander Fleming", Institute for 
      Bioinnovation, Vari, Greece.
FAU - Makatounakis, Takis
AU  - Makatounakis T
AD  - Institute of Molecular Biology and Biotechnology (IMBB), Foundation for Research 
      and Technology-Hellas (FORTH), Crete, Greece.
FAU - Kretsovali, Androniki
AU  - Kretsovali A
AUID- ORCID: 0000-0003-2949-1619
AD  - Institute of Molecular Biology and Biotechnology (IMBB), Foundation for Research 
      and Technology-Hellas (FORTH), Crete, Greece.
FAU - Papamatheakis, Joseph
AU  - Papamatheakis J
AUID- ORCID: 0000-0003-4553-2601
AD  - Institute of Molecular Biology and Biotechnology (IMBB), Foundation for Research 
      and Technology-Hellas (FORTH), Crete, Greece.
AD  - Department of Biology, University of Crete, Heraklion, Greece.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230904
PL  - United States
TA  - Mol Oncol
JT  - Molecular oncology
JID - 101308230
RN  - 0 (Promyelocytic Leukemia Protein)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Humans
MH  - Female
MH  - *Breast Neoplasms/pathology
MH  - Promyelocytic Leukemia Protein/genetics
MH  - Vascular Endothelial Growth Factor A
MH  - Cell Line, Tumor
MH  - Epithelial-Mesenchymal Transition/genetics
MH  - Transcription Factors/genetics
MH  - Cell Movement
PMC - PMC10552902
OTO - NOTNLM
OT  - EMT
OT  - PML
OT  - angiogenesis
OT  - breast cancer
OT  - metastasis
OT  - transcriptomics
COIS- The authors declare no conflict of interest.
EDAT- 2023/07/31 06:42
MHDA- 2023/10/06 06:43
PMCR- 2023/09/04
CRDT- 2023/07/31 01:23
PHST- 2023/06/05 00:00 [revised]
PHST- 2023/03/02 00:00 [received]
PHST- 2023/07/28 00:00 [accepted]
PHST- 2023/10/06 06:43 [medline]
PHST- 2023/07/31 06:42 [pubmed]
PHST- 2023/07/31 01:23 [entrez]
PHST- 2023/09/04 00:00 [pmc-release]
AID - MOL213501 [pii]
AID - 10.1002/1878-0261.13501 [doi]
PST - ppublish
SO  - Mol Oncol. 2023 Oct;17(10):2090-2108. doi: 10.1002/1878-0261.13501. Epub 2023 Sep 
      4.