A Homeobox Protein, Prox1, Is Involved in the Differentiation, Proliferation, and Prognosis in Hepatocellular Carcinoma

Abstract

Purpose: It has been shown that a lymphatic differentiation master gene, prox1, also plays an essential role in fetal hepatocyte migration. Its expression is detected in embryonic hepatoblasts and in adult hepatocytes. Hepatoma cells are similar to embryonic hepatoblasts to a certain extent because they both proliferate and invade the surrounding tissue. To address the possibility that Prox1 may be involved in the tumorigenesis of hepatocellular carcinoma (HCC), human clinical samples were analyzed. Experimental Design: To screen prox1 as a potential tumor suppressor gene, its expression was analyzed in HCC cell lines and in human HCC tissues. Its growth-conferring abilities were assessed by transiently overexpressing Prox1in HCC cell lines and by knocking down its expression by RNA interference. Results: We found that there was a significant correlation between Prox1 expression and the differentiation scores of the tumors. Subsequently, we also showed that low expression of Prox1 in tumors was closely associated with a poor prognosis.The specific knockdown of Prox1by RNA interference strongly accelerated in vitro cell growth, whereas the overexpression of Prox1greatly suppressed the growth. Conclusions: Our results suggest that Prox1is involved in the differentiation and progression of HCC, and thus it may be a candidate for the development of novel diagnostic and therapeutic strategies for HCC.

The homeobox transcription factor Prox1 inhibits proliferation of hepatocellular carcinoma cells by inducing p53-dependent senescence-like phenotype

“…Recent studies demonstrated that reduction of Prox1 was found in HCC tissues and low expression of Prox1 was associated with poor prognosis and un-differentiation status. 24,25 These data implicate a potential tumor suppressor role of Prox1 in HCC. However, the underlying mechanism by which Prox1 inhibits the development of HCC is unknown.…”

“…The study of functional role of Prox1 in HCC was first reported by Shimoda et al 24 They showed that Prox1 expression was associated with the differentiation status of HCC tumors. Figure 5A, Twist reversed the increase of β-galactosidase-positive cells induced by Prox1.…”

Fluorescence in Situ Hybridization Markers for Prediction of Cervical Lymph Node Metastases

“…14,33,34 Decreased PROX1 expression has been found in several cancers, including hepatocellular carcinoma, biliary duct cancer, and breast cancer. [35][36][37] However, in colon cancer, overexpression of PROX1 induces colon cancer progression by promoting a transition from a benign to a highly dysplastic phenotype. 38 In cervical cancer, PROX1 lies within a region of amplification (chromosome 1q) which could suggest that PROX1 copy number gain may function similarly to that in colon cancer.…”

Prospero homeobox 1 mediates the progression of gastric cancer by inducing tumor cell proliferation and lymphangiogenesis

“…PROX1 plays multifunctional roles in human cancers and acts as a tumor suppressor gene or an oncogene based on the cancer type, thus exerting variable effects on cell proliferation and differentiation [8]. Decreased expression of PROX1 is observed in pancreatic cancers, hepatocellular carcinomas, sporadic breast cancers, and biliary carcinomas, indicating that PROX1 plays a tumor-suppressive role in these cancers [9][10][11][12]. In contrast, overexpression of PROX1 is observed in colorectal cancers, endothelial tumors, and gliomas, indicating that PROX1 promotes the progression of these cancers [13][14][15][16].…”