Transforming growth factor beta signaling in hepatocellular carcinoma: as a victim or culprit?

Varun Kumar Sharma, Charu Tyagi, Yugandhar P. Reddy, Jayanand Manjhi, Lomas Kumar Tomar


The transforming growth factor-β (TGFβ) signalling pathway control various cellular function and play a pivotal role in tumour suppression. In contrary, overexpression of TGFβ is linked to promote the cancer development. TGFβ facilitate cell-growth and cell-differentiation process which support tumour propagation. In case of hepatocellular carcinoma (HCC), TGFβ signalling pathway is the master regulator of HCCs pathogenesis and functionally involved in the regulation of HCCs phenotype via modulating the downstream signalling pathways. In this article, we have highlighted the contradictory behaviour of TGFβ in hepatocellular carcinoma. Observations suggest that the TGFβ signalling pathway is positively correlated to the expression of genes linked with various hepatic pathological conditions, including fibrosis, cirrhosis, inflammation and cancer. TGFβ pathway play dual role as pro and anti-tumoural activities in cancer cells depending on their context.


Hepatocellular carcinoma, Signaling pathway, Transforming growth factor-β

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Massagué J. TGFbeta in Cancer. Cell. 2008 Jul;134:215-30.

Frick CL, Yarka C, Nunns H, Goentoro L. Sensing relative signal in the Tgf-β/Smad pathway. Proc Natl Acad Sci USA. 2017 Apr;114:2975-82.

David CJ, Huang YH, Chen M, Su J, Zou Y, Bardeesy N, et al. TGF-β Tumor Suppression through a Lethal EMT. Cell. 2016 Feb;164:1015-30.

Zhang L, Zhou F, ten Dijke P. Signaling interplay between transforming growth factor-β receptor and PI3K/AKT pathways in cancer. Trends Biochem Sci. 2013 Dec;38:612-20.

Chen J, Zaidi S, Rao S, Chen JS, Phan L, Farci P, et al. Analysis of Genomes and Transcriptomes of Hepatocellular Carcinomas Identifies Mutations and Gene Expression Changes in the Transforming Growth Factor-β Pathway. Gastroenterology. 2018 Jan;154:195-210.

Chen J, Yao ZX, Chen JS, Gi YJ, Muñoz NM, Kundra S, et al. TGF-β/β2-spectrin/CTCF-regulated tumor suppression in human stem cell disorder Beckwith-Wiedemann syndrome. J Clin Invest. 2016 Feb;126:527-42.

Wang L, Zhang Z, Wang FS. The efficacy of miRNA122, a novel therapeutic target, for predicting the progression of hepatocellular carcinoma (HCC). Cell MolImmunol. 2012 Mar;9:103-4.

Sharma VK, Kaveri SV, Bayry J. Impaired regulatory T cell function in autoimmune diseases: are microRNAs the culprits? Cell MolImmunol. 2016 Mar;13:135-7.

Chen J, Shukla V, Farci P, Andricovich J, Jogunoori W, Kwong LN, et al. Loss of the transforming growth factor-β effector β2-Spectrin promotes genomic instability. Hepatology. 2017 Feb;65:678-93.

Cancer Genome Atlas Research Network. Comprehensive and Integrative Genomic Characterization of Hepatocellular Carcinoma. Cell. 2017 Jun;169:1327-41.