PMID- 37361585
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230701
IS  - 2234-943X (Print)
IS  - 2234-943X (Electronic)
IS  - 2234-943X (Linking)
VI  - 13
DP  - 2023
TI  - AATF inhibition exerts antiangiogenic effects against human hepatocellular 
      carcinoma.
PG  - 1130380
LID - 10.3389/fonc.2023.1130380 [doi]
LID - 1130380
AB  - BACKGROUND AND AIMS: Angiogenesis is a key factor in the growth and metastasis of 
      hepatic tumors and thus a potential therapeutic target in hepatocellular 
      carcinoma (HCC). In this study, we aim to identify the key role of apoptosis 
      antagonizing transcription factor (AATF) in tumor angiogenesis and its underlying 
      mechanisms in HCC. METHODS: HCC tissues were analyzed for AATF expression by 
      qRT-PCR and immunohistochemistry. Stable clones of control and AATF knockdown 
      (KD) were established in human HCC cells. The effect of AATF inhibition on the 
      angiogenic processes was determined by proliferation, invasion, migration, chick 
      chorioallantoic membrane (CAM) assay, zymography, and immunoblotting techniques. 
      RESULTS: We identified high levels of AATF in human HCC tissues compared to 
      adjacent normal liver tissues, and the expression was found to be correlated with 
      the stages and tumor grades of HCC. Inhibiting AATF in QGY-7703 cells resulted in 
      higher levels of pigment epithelium-derived factor (PEDF) than controls due to 
      decreased matric metalloproteinase activity. Conditioned media from AATF KD cells 
      inhibited the proliferation, migration, and invasion of human umbilical vein 
      endothelial cells as well as the vascularization of the chick chorioallantoic 
      membrane. Furthermore, the VEGF-mediated downstream signaling pathway responsible 
      for endothelial cell survival and vascular permeability, cell proliferation, and 
      migration favoring angiogenesis was suppressed by AATF inhibition. Notably, PEDF 
      inhibition effectively reversed the anti-angiogenic effect of AATF KD. 
      CONCLUSION: Our study reports the first evidence that the therapeutic strategy 
      based on the inhibition of AATF to disrupt tumor angiogenesis may serve as a 
      promising approach for HCC treatment.
CI  - Copyright (c) 2023 Suresh, Srinivas, Prashant, Satish, Vishwanath, Nataraj, Koduru, 
      Santhekadur and Kumar.
FAU - Suresh, Diwakar
AU  - Suresh D
AD  - Department of Biochemistry, CEMR, JSS Medical College, JSS Academy of Higher 
      Education and Research, Mysuru, Karnataka, India.
FAU - Srinivas, Akshatha N
AU  - Srinivas AN
AD  - Department of Biochemistry, CEMR, JSS Medical College, JSS Academy of Higher 
      Education and Research, Mysuru, Karnataka, India.
FAU - Prashant, Akila
AU  - Prashant A
AD  - Department of Biochemistry, CEMR, JSS Medical College, JSS Academy of Higher 
      Education and Research, Mysuru, Karnataka, India.
FAU - Satish, Suchitha
AU  - Satish S
AD  - Department of Pathology, JSS Medical College and Hospital, JSS Academy of Higher 
      Education and Research, Mysuru, India.
FAU - Vishwanath, Prashant
AU  - Vishwanath P
AD  - Department of Biochemistry, CEMR, JSS Medical College, JSS Academy of Higher 
      Education and Research, Mysuru, Karnataka, India.
FAU - Nataraj, Suma M
AU  - Nataraj SM
AD  - Department of Biochemistry, CEMR, JSS Medical College, JSS Academy of Higher 
      Education and Research, Mysuru, Karnataka, India.
FAU - Koduru, Srinivas V
AU  - Koduru SV
AD  - Gene Arrays, Omelette Inc., New York, NY, United States.
FAU - Santhekadur, Prasanna K
AU  - Santhekadur PK
AD  - Department of Biochemistry, CEMR, JSS Medical College, JSS Academy of Higher 
      Education and Research, Mysuru, Karnataka, India.
FAU - Kumar, Divya P
AU  - Kumar DP
AD  - Department of Biochemistry, CEMR, JSS Medical College, JSS Academy of Higher 
      Education and Research, Mysuru, Karnataka, India.
LA  - eng
PT  - Journal Article
DEP - 20230609
PL  - Switzerland
TA  - Front Oncol
JT  - Frontiers in oncology
JID - 101568867
PMC - PMC10288852
OTO - NOTNLM
OT  - angiogenesis
OT  - apoptosis antagonizing transcription factor
OT  - hepatocellular carcinoma
OT  - human umbilic vein endothelial cells (HUVEC)
OT  - knockdown (KD)
OT  - pigment epithelium derived factor
COIS- Author SK was employed by Omelette Inc. The remaining authors declare that the 
      research was conducted in the absence of any commercial or financial 
      relationships that could be construed as a potential conflict of interest.
EDAT- 2023/06/26 19:07
MHDA- 2023/06/26 19:08
PMCR- 2023/01/01
CRDT- 2023/06/26 12:54
PHST- 2022/12/23 00:00 [received]
PHST- 2023/05/26 00:00 [accepted]
PHST- 2023/06/26 19:08 [medline]
PHST- 2023/06/26 19:07 [pubmed]
PHST- 2023/06/26 12:54 [entrez]
PHST- 2023/01/01 00:00 [pmc-release]
AID - 10.3389/fonc.2023.1130380 [doi]
PST - epublish
SO  - Front Oncol. 2023 Jun 9;13:1130380. doi: 10.3389/fonc.2023.1130380. eCollection 
      2023.