NEDD4 promotes cell growth and motility in hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related death worldwide. In China, the situation is even worse as cancer incidence and mortality continue to increase rapidly. Although tremendous progress has been made toward HCC treatments, the benefits for liver cancer patients are still limited. Therefore, it is necessary to identify and develop novel therapeutic methods. Neuronally expressed developmentally downregulated 4 (NEDD4), an E3 ubiquitin ligase, plays a critical role in the development and progression of various types of human cancers. In our study, NEDD4 acts as an oncoprotein in both QGY7703 and SMMC7721 liver cancer cell lines. We found that depletion of NEDD4 by siRNA transfection led to inhibition of cell growth, invasion and migration, and promotion of apoptosis. In contrast, overexpression of NEDD4 via plasmid transfection resulted in facilitated cell proliferation, invasion and migration, and decreased apoptosis. Importantly, we observed that tumor suppressor LATS1, also a core component of Hippo pathway, was negatively regulated by NEDD4 in liver cancer cells. Our findings suggested that NEDD4 may be involved in the HCC progression via regulating LATS1 associated signaling pathway. Therefore, targeting NEDD4-LATS1 signaling could be a potential therapeutic option for HCC treatment.

NEDD4 expression is associated with breast cancer progression and is predictive of a poor prognosis

“…Cumulative evidence suggests that NEDD4 is linked to tumor progression in several human cancers, such as gastric carcinoma, hepatoma carcinoma, bladder cancer, and prostate cancer [25, 32, 33, 38]. Based on our studies, NEDD4 expression gradually increases in line with BC progression, from normal tissues, DCIS, IDC without lymph node metastasis to BCLNM tumors, which is a well-established clinical model for BC progression [5].…”

“…NEDD4 has a role in promoting the growth of hepatocellular [32] and bladder cancer cell lines [33]. To determine the role of NEDD4 in BC growth, we first examined how NEDD4 expression affects cell growth using BC cell lines from different BC subtypes.…”

ACOX2 is a prognostic marker and impedes the progression of hepatocellular carcinoma via PPARα pathway

“…Chronic inflammation infection, mainly caused by hepatitis B virus (HBV) or hepatitis C virus (HCV), has been proposed as a causative mechanism in HCC carcinogenesis 4 . Although the diagnosis and treatment methods of HCC have been developing, exairesis is still the first line and most effective treatment to HCC 5 . What is frustrating is that the recurrence and mortality of HCC is still high because of the extensive characteristics of HCC, including intrahepatic metastasis, venous invasion, and distant metastasis 6 .…”

Functional roles of E3 ubiquitin ligases in gastric cancer (Review)

“…NEDD4-1 contains four WW domains and is an ancestral member of the NEDD4 family ( 23 ). Previous studies have indicated that NEDD4-1 is frequently overexpressed in several types of human cancers, including hepatocellular carcinoma, lung cancer and gastrointestinal cancer ( 128 – 130 ). A range of tumor suppressors can be ubiquitinated by NEDD4-1, including PTEN, c-Myc and large tumor suppressor kinase 1 ( 128 , 131 ).…”

“…Previous studies have indicated that NEDD4-1 is frequently overexpressed in several types of human cancers, including hepatocellular carcinoma, lung cancer and gastrointestinal cancer ( 128 – 130 ). A range of tumor suppressors can be ubiquitinated by NEDD4-1, including PTEN, c-Myc and large tumor suppressor kinase 1 ( 128 , 131 ). Immunohistochemical analysis conducted by Kim et al ( 130 ) showed that NEDD4-1 is overexpressed in colorectal and gastric carcinomas.…”