Document Type : Original Article
Authors
1
Departments of Internal Medical, Shiraz University of Medical Sciences, Shiraz, Iran.
2
Ahl Al Bayt University, Kerbala, Iraq.
3
Collage of Pharmacy, National University of Science and Technology, Dhi Qar, 64001, Iraq.
4
Department of Medicine, Zabol University of Medical Science, Zabol, Iran.
5
Gilgamesh Ahliya University, Baghdad, Iraq .
6
Department of Pharmacy, Al-Zahrawi University College, Karbala, Iraq .
7
Pharmacy college, Al-Farahidi University, Iraq .
8
Department of Biology, Faculty of Sciences, Shahid Chamran University of Ahvaz, Ahvaz, Iran .
9
Department of Surgical Oncology, Tehran University of Medical Medicine, Tehran, Iran
Abstract
A key component of the Hippo signaling pathway (HSP) is a kinase cascade that connects
the tumor suppressor Hippo to the oncoprotein Yki (YAP and TAZ). This oncoprotein
functions as a transcriptional coactivator for target genes that play critical roles in cell
proliferation and survival. The objective of this study is to evaluate the interaction
between TGF-β proteins and key components of the Hippo signaling pathway in
regulating hepatocellular carcinoma (HCC) cell behavior. One important achievement of
this study was to reveal the significant inhibitory role of the HSP in the growth of HCC
cells through TGF-β proteins. In the present study, we examined the expression of key
proteins of the Hippo pathway in HCC cells treated with TGF-β proteins and their
correlation with the Hippo signaling pathway (HSP) by immunofluorescent staining,
immunoblotting method, and Real-time PCR. Both Yes‑ associated protein (YAP) and
large tumor suppressor 1 (LATS1) were correlated with HCC cells. In the HSP, LATS1
plays as an upstream inhibitory agent of YAP. Nucleus-cytoplasm translocation of YAP1
and overexpression of LATS1 occurred in HCC cells treated with TGF-β. The
nucleocytoplasmic distribution of YAP1 and overexpression of LATS1 have anti-
oncogenetic roles in the incidence and progression of HCC. TGF-β in 5 ng/mL treatment
resulted in a 2.5-fold increase in LATS1 expression and significant YAP1 translocation
from the nucleus to the cytoplasm. We concluded that the Hippo signaling pathway
mediates TGF-β/TBR-induced effects on HCC progression.
Keywords: Transforming growth factor-beta (TGF-β), Hepatocellular carcinoma (HCC),
Salvador-Warts-Hippo (SWH) pathway, Hippo signaling pathway (HSP
Keywords