30 These integrins, which are subjected to differential spatio-temporal glycosylation on distinct cell types,31 play an essential role in cell adhesion, migration, local invasion,

and metastatic dissemination of HCC cells.32, 33 Our results show that Gal-1 exerts its effects on HepG2 cell adhesion through interaction with α1, α2, α3, αV, and/or β1 integrins, suggesting that high levels of Gal-1 in liver tumors microenvironment may contribute to cell adhesion to ECM through interaction with such integrins, thus favoring HCC progression. Accordingly, overexpression of Gal-1 has been found find more in the stroma of HCC tumors and during metastatic seeding.11 The binding of integrins to ECM substrates can lead to the activation of various signaling cascades, such as

HDAC inhibitor Akt and ERK1/2 pathways.34 Here, we demonstrate that PI3K and/or ERK1/2 MAPK signaling pathways are involved in HCC cell adhesion promoted by Gal-1. Similarly, Gal-1 also favors adhesion of human colon cancer cells to the ECM in a PI3K and/or ERK1/2 MAPK-dependent manner.35 Development of polarity is critical for hepatocyte function. Here, we show that, as a consequence of favoring cell adhesion, Gal-1 promotes BC development through modulation of PI3K, ERK1/2 MAPK, and PKA signaling pathways. This effect does not interfere with MDR1 or MRP2 apical localization or canalicular secretory function, at least through MRP2. Interestingly,

signaling pathways induced by Gal-1 resemble those involved in the integrin/PI3K-dependent exocytic insertion of canalicular transporters promoted by tauroursodeoxycholate, a stimulator of canalicular secretion.36 Gal-1 is involved in various stages of tumor progression, including cell adhesion, migration, angiogenesis, and immune escape, and has therefore been described as a promising cancer target. Here, we demonstrate that Gal-1 up-regulation in the liver tumor 上海皓元 microenvironment favors HCC growth and metastasis. Perturbation of cell polarity is an important hallmark of advanced invasive tumors, and cross-talk between oncogenic signals and polarity regulatory proteins has been described.37 Taken together, our findings highlight a novel role for an endogenous lectin in liver pathophysiology and HCC progression through coupling cell adhesion and polarization processes. rGal-3 was a gift from N. Panjwani. We thank D. Compagno and D. Laderach for technical assistance and M. C. Larocca, M. G. Roma, R. Marinelli, and A. D. Mottino for helpful suggestions. Additional Supporting Information may be found in the online version of this article. “
“Objective and Background:  The onset of IBS is in adolescence in many cases. However, the features of adolescent IBS were generally lacking. The objective of this research was to know the features of adolescent IBS in Japan.