Four Major Factors Contributing to Intrahepatic Stones

Intrahepatic stone is prevalent in Asian countries; though the incidence declines in recent years, the number of patients is still in a large quantity. Because of multiple complications, high recurrence rates, serious systemic damage, and a lack of extremely effective procedure for the management, it is more important to find out the etiology and pathogenesis of intrahepatic stones to prevent the disease from happening and developing rather than curing. A number of factors contribute to the development of the disease, such as cholestasis, infection, and anatomic abnormity of bile duct and bile metabolic defect. The four factors and possible pathogenesis will be discussed in detail in the review

Four Major Factors Contributing to Intrahepatic Stones

Intrahepatic stone is prevalent in Asian countries; though the incidence declines in recent years, the number of patients is still in a large quantity. Because of multiple complications, high recurrence rates, serious systemic damage, and a lack of extremely effective procedure for the management, it is more important to find out the etiology and pathogenesis of intrahepatic stones to prevent the disease from happening and developing rather than curing. A number of factors contribute to the development of the disease, such as cholestasis, infection, and anatomic abnormity of bile duct and bile metabolic defect. The four factors and possible pathogenesis will be discussed in detail in the review

LMO3 promotes hepatocellular carcinoma invasion, metastasis and anoikis inhibition by directly interacting with LATS1 and suppressing Hippo signaling

Abstract Background In this research, we aimed to investigate the biological functions of LIM domain only 3 (LMO3) in hepatocellular carcinoma (HCC) and uncover the underlying molecular mechanism in it. Methods HCC tissue microarray (n = 180) was used to analyze the correlation between LMO3 expression and clinicopathological findings. In vitro transwell matrigel invasion assay and annexin V anoikis assay in HCC cells were conducted to investigate LMO3 related biological functions. In vivo intrahepatic and lung metastasis models were used to determine the role of LMO3 in HCC metastasis. Quantitative real-time PCR, western blotting and immunohistochemical staining were performed to investigate the expression and mechanism of LMO3 in HCC. Results We found that the expression of LMO3 was significantly upregulated in HCC tissues, and it was closely related to clinicopathological findings and patient prognoses. Knockdown of LMO3 suppressed the invasion and anoikis inhibition of HCC cells in vitro. Meanwhile, the metastasis of SMMC-7721 cells was also suppressed by LMO3 knockdown in vivo. Furthermore, we found that LMO3 knockdown increased the phosphorylation of YAP and LATS1, and decrease Rho GTPases activities. LMO3 directly interacted with LATS1, and thus suppressed Hippo signaling. Recombinant LMO3 (rLMO3) protein administration decreased the phosphorylation of YAP and LATS1, and increased Rho GTPases activities. The inhibitors of the Hippo pathway abrogated rLMO3 protein-induced HCC cell invasion and anoikis inhibition. Conclusions These results suggest that LMO3 promotes HCC cell invasion and anoikis inhibition by interacting with LATS1 and suppressing Hippo signaling. LMO3 may serve as a potential therapeutic target for HCC in future