Retinoic acid receptors (RAR; α, β, and γ), members of the nuclear receptor superfamily, mediate the pleiotropic effects of the vitamin A metabolite retinoic acid (RA) and derivatives (retinoids) in normal and cancer cells. Abnormal expression and function of RARs are often involved in the growth and development of cancer. However, the underlying molecular mechanisms remain largely elusive. Here, we report that levels of RARγ were significantly elevated in tumor tissues from a majority of human hepatocellular carcinoma (HCC) and in HCC cell lines. Overexpression of RARγ promoted colony formation by HCC cells in vitro and the growth of HCC xenografts in animals. In HepG2 cells, transfection of RARγ enhanced, whereas downregulation of RARγ expression by siRNA approach impaired, the effect of RA on inducing the expression of α-fetoprotein, a protein marker of hepatocarcinogenesis. In studying the possible mechanism by which overexpression of RARγ contributed to liver cancer cell growth and transformation, we observed that RARγ resided mainly in the cytoplasm of HCC cells, interacting with the p85α regulatory subunit of phosphatidylinositol 3-kinase (PI3K). The interaction between RARγ and p85α resulted in activation of Akt and NF-κB, critical regulators of the growth and survival of cancer cells. Together, our results show that overexpression of RARγ plays a role in the growth of HCC cells through nongenomic activation of the PI3K/Akt and NF-κB signaling pathways. Cancer Res; 70(6); 2285–95

The Optimum Multiparameter (OMP) method was used to determine the relative contribution of water masses in the East China Sea (ECS) based on their measured temperature, salinity, and dissolved inorganic iodine species (DIIS, iodate and iodide) from recent oceanographic cruises in June 2014, 2015, and 2016. DIIS (as quasi‐conservative parameters) were added first into the OMP analysis, which enabled us to quantitatively estimate the water composition in the extremely dynamic and productive ECS. The OMP results indicate that seawater in the ECS mainly consisted of Changjiang Diluted Water (CDW), Taiwan Strait Warm Water (TSWW), Kuroshio Surface Water (KSW), and Kuroshio Subsurface Water (KSSW). In June 2014, 2015, and 2016, the KSSW dominated in the deep water, intruded into the ECS shelf from the northeast of Taiwan and bifurcated into a nearshore branch and offshore branch. The nearshore branch could reach north of 29°N off the Zhejiang coast. When comparing the KSSW intrusion in June 2014, 2015, and 2016, the average KSSW contribution of the bottom KSSW area in June 2016 (78.9%) was greater than in the previous 2 years (67.9% and 64.5%). In the northern transects (north of 28°N), the KSSW intrusion in June 2016 also contained the greatest average KSSW contribution and the maximum coverage area. Thus, the KSSW intrusion was strongest in June 2016 and may be comparable in June 2014 and 2015. This interannual variability of the KSSW intrusion is likely related to the El Niño‐Southern Oscillation (ENSO) rather than the Pacific Decadal Oscillation (PDO).