1-3 Knowledge of the oncogenic processes and the signaling pathways regulating HCC cell proliferation, survival, invasion, and metastasis has led to the development of targeted therapies with positive results, as exemplified by the multitarget inhibitor, sorafenib.2 However, notwithstanding the survival

benefits of sorafenib, there is still room for improvement, and current research is aiming to combine molecular therapies. To this end, increasing knowledge on the signaling pathways critical for HCC progression is of crucial importance. Connective tissue growth factor (CTGF) is a cysteine-rich secreted protein that interacts with a variety RO4929097 ic50 of extracellular matrix components and cell-surface proteins, such as fibronectin, proteoglycans, and integrins, strongly influencing cellular behavior.4 CTGF participates in many biological processes, including cell proliferation, survival, migration, angiogenesis, wound healing, and cancer development.4-6 In the liver, CTGF has been recognized as a key profibrogenic factor, its expression is increased in fibrotic human and rat liver, and the manipulation of CTGF levels in experimental CB-839 cell line fibrosis modulates the course of the disease.6 More recently, CTGF expression was reported

to be elevated in HCC tissues, and HCC patients with high serum CTGF levels show reduced survival, attesting to the potential relevance of CTGF in HCC progression.7, 8 Transforming growth factor beta (TGF-β) is

regarded as the major inducer of CTGF expression, and evidence suggests that CTGF, indeed, mediates many of the pathological effects of TGF-β in liver disease, including fibrosis development and HCC progression.4, 9 In view of all selleck products this, the understanding of CTGF regulation and biological effects in liver cancer cells would be important for the characterization of this factor as a molecular target in HCC. Previously, we demonstrated that CTGF expression in experimental liver fibrosis was affected by the epidermal growth factor receptor (EGFR) ligand, amphiregulin (AR), and that AR directly promoted CTGF expression in human and mouse fibrogenic cells.10 Signaling through the EGFR is regarded as an important mechanism in hepatocarcinogenesis and as a target for molecular therapies.2, 3, 11 Here, we demonstrate that CTGF expression in HCC cells participates in cell proliferation, survival, and inflammatory gene expression and is regulated by EGFR activation in a novel cross-talk with the oncogenic transcriptional coactivator, Yes-associated protein (YAP).