NDLI: Comparative Analysis of TGF-β/Smad Signaling Dependent Cytostasis in Human Hepatocellular Carcinoma Cell Lines

Content Provider	PubMed Central
Author	Johanna, Dzieran Fabian, Jasmin Feng, Teng Coulouarn, Cédric Ilkavets, Iryna Anastasia, Kyselova Kai, Breuhahn Dooley, Steven Meindl-beinker, Nadja M.
Editor	Katoh, Masaru
Copyright Year	2013
Abstract	Hepatocellular carcinoma (HCC) is a major public health problem due to increased incidence, late diagnosis and limited treatment options. TGF-β is known to provide cytostatic signals during early stages of liver damage and regeneration, but exerts tumor promoting effects in onset and progression of liver cancer. To understand the mechanistic background of such a switch, we systematically correlated loss of cytostatic TGF-β effects with strength and dynamics of its downstream signaling in 10 HCC cell lines. We demonstrate that TGF-β inhibits proliferation and induces apoptosis in cell lines with low endogenous levels of TGF-β and Smad7 and strong transcriptional Smad3 activity (PLC/PRF/5, HepG2, Hep3B, HuH7), previously characterized to express early TGF-β signatures correlated with better outcome in HCC patients. TGF-β dependent cytostasis is blunted in another group of cell lines (HLE, HLF, FLC-4) expressing high amounts of TGF-β and Smad7 and showing significantly reduced Smad3 signaling. Of those, HLE and HLF exhibit late TGF-β signatures, which is associated with bad prognosis in HCC patients. RNAi with Smad3 blunted cytostatic effects in PLC/PRF/5, Hep3B and HuH7. HCC-M and HCC-T represent a third group of cell lines lacking cytostatic TGF-β signaling despite strong and prolonged Smad3 phosphorylation and low Smad7 and TGF-β expression. Inhibitory linker phosphorylation, as in HCC-T, may disrupt C-terminally phosphorylated Smad3 function. In summary, we assort 10 HCC cell lines in at least two clusters with respect to TGF-β sensitivity. Cell lines responsive to the TGF-β cytostatic program, which recapitulate early stage of liver carcinogenesis exhibit transcriptional Smad3 activity. Those with disturbed TGF-β/Smad3 signaling are insensitive to TGF-β dependent cytostasis and might represent late stage of the disease. Regulation of this switch remains complex and cell line specific. These features may be relevant to discriminate stage dependent TGF-β functions for the design of efficient TGF-β directed therapy in liver cancer.
Related Links	http://dx.doi.org/10.1371/journal.pone.0072252
Starting Page	72252
File Format	PDF
ISSN	19326203
e-ISSN	19326203
Journal	PLoS ONE
Issue Number	8
Volume Number	8
Language	English
Publisher	Public Library of Science
Publisher Date	2013-08-01
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Agricultural and Biological Sciences(all) Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Correction: Comparative Analysis of TGF-β/Smad Signaling Dependent Cytostasis in Human Hepatocellular Carcinoma Cell Lines

Comparative Analysis of TGF-β/Smad Signaling Dependent Cytostasis in Human Hepatocellular Carcinoma Cell Lines

Constraint-Based Modeling and Kinetic Analysis of the Smad Dependent TGF-β Signaling Pathway

The Role of TGF-β/SMAD Signaling in Hepatocellular Carcinoma: from Mechanism to Therapy and Prognosis

Essential Role of TGF-β/Smad Pathway on Statin Dependent Vascular Smooth Muscle Cell Regulation

Targeting the Wnt/β-Catenin Signaling Pathway in Liver Cancer Stem Cells and Hepatocellular Carcinoma Cell Lines with FH535

TGF-β Signaling Is Often Attenuated during Hepatotumorigenesis, but Is Retained for the Malignancy of Hepatocellular Carcinoma Cells

Effects of TRAP-1-Like Protein (TLP) Gene on Collagen Synthesis Induced by TGF-β/Smad Signaling in Human Dermal Fibroblasts

TGF-Beta Induced Erk Phosphorylation of Smad Linker Region Regulates Smad Signaling

Comparative Analysis of TGF-β/Smad Signaling Dependent Cytostasis in Human Hepatocellular Carcinoma Cell Lines

Similar Documents

Correction: Comparative Analysis of TGF-β/Smad Signaling Dependent Cytostasis in Human Hepatocellular Carcinoma Cell Lines

Comparative Analysis of TGF-β/Smad Signaling Dependent Cytostasis in Human Hepatocellular Carcinoma Cell Lines

Constraint-Based Modeling and Kinetic Analysis of the Smad Dependent TGF-β Signaling Pathway

The Role of TGF-β/SMAD Signaling in Hepatocellular Carcinoma: from Mechanism to Therapy and Prognosis

Essential Role of TGF-β/Smad Pathway on Statin Dependent Vascular Smooth Muscle Cell Regulation

Targeting the Wnt/β-Catenin Signaling Pathway in Liver Cancer Stem Cells and Hepatocellular Carcinoma Cell Lines with FH535

TGF-β Signaling Is Often Attenuated during Hepatotumorigenesis, but Is Retained for the Malignancy of Hepatocellular Carcinoma Cells

Effects of TRAP-1-Like Protein (TLP) Gene on Collagen Synthesis Induced by TGF-β/Smad Signaling in Human Dermal Fibroblasts

TGF-Beta Induced Erk Phosphorylation of Smad Linker Region Regulates Smad Signaling

Comparative Analysis of TGF-β/Smad Signaling Dependent Cytostasis in Human Hepatocellular Carcinoma Cell Lines