RESUMO
Unlike healthy, non-transformed cells, the proteostasis network of cancer cells is taxed to produce proteins involved in tumor development. Cancer cells have a higher dependency on molecular chaperones to maintain proteostasis. The chaperonin T-complex protein ring complex (TRiC) contains eight paralogous subunits (CCT1-8), and assists the folding of as many as 10% of cytosolic proteome. TRiC is essential for the progression of some cancers, but the roles of TRiC subunits in osteosarcoma remain to be explored. Here, we show that CCT4/TRiC is significantly correlated in human osteosarcoma, and plays a critical role in osteosarcoma cell survival. We identify a compound anticarin-β that can specifically bind to and inhibit CCT4. Anticarin-β shows higher selectivity in cancer cells than in normal cells. Mechanistically, anticarin-β potently impedes CCT4-mediated STAT3 maturation. Anticarin-β displays remarkable antitumor efficacy in orthotopic and patient-derived xenograft models of osteosarcoma. Collectively, our data uncover a key role of CCT4 in osteosarcoma, and propose a promising treatment strategy for osteosarcoma by disrupting CCT4 and proteostasis.
RESUMO
Objective To analyze the epidemiological characteristics of patients with sea lice injury in coastal baths in Qinhuangdao City, and provide scientific evidence for the importance of prevention of sea lice injury and the early warning of sea lice outbreak. Methods The data of 2 659 patients with sea lice injury, including gender, age composition, severity of bruises and other epidemiological data reported by the coastal bathing stations in Qinhuangdao City from 2016 to 2018 (mainly from July to August) were retrospectively analyzed, and the correlation between the temperature at the surface of sea water and the number of patients with sea lice injury was also analyzed. Results Among the 7 bathing beaches along the coast of Qinhuangdao City, Dongshan Bathing Spot (1 101 cases) and Repulse Bay Bathing Beach (1 365 cases) had the largest numbers of bruises, while the Gold Coast Bath had the least (only 5 cases), and the differences in number of bruises in different baths were statistically significant in 2016, 2017, 2018 years (277, 1 890, 492 cases respectively, χ2= 490.611, P < 0.05). Among 2 659 patients, 1 124 were children (≤14 years old), 1 535 were adult, 1 570 male and 1 089 female patients. The severity type of patients' sea lice injury in each bath was mainly mild to moderate type; among the total injury cases, there were 2 589 cases with mild type injury accounting for 97.37%, 61 cases with moderate type (2.29%) and 9 cases with severe type (0.34%). A linear trend between sea surface temperature and the patients' number of bruises was seen, and there was a positive correlation between the sea surface temperature and the patients' number (r = 0.433, P < 0.05). Conclusion The sea lice injuries in Qinhuangdao City are mainly distributed in the Dongshan and Repulse Bay Baths, the main type of injury is light one, and in the mean time the injury is influenced by factors such as popularization of science, medical care, environmental factors, and collective sea lice drift, etc.