A polarity complex of PAR-3, PAR-6, and atypical protein kinase C (aPKC) functions in various cell polarization events. PAR-3 directly interacts with Tiam1/Taim2 (STEF), Rac1-specific guanine nucleotide exchange factors, and forms a complex with aPKC-PAR-6-Cdc42*GTP, leading to Rac1 activation. RhoA antagonizes Rac1 in certain types of cells. However, the relationship between RhoA and the PAR complex remains elusive. We found here that Rho-kinase/ROCK/ROK, the effector of RhoA, phosphorylated PAR-3 at Thr833 and thereby disrupted its interaction with aPKC and PAR-6, but not with Tiam2. Phosphorylated PAR-3 was observed in the leading edge, and in central and rear portions of migrating cells having front-rear polarity. Knockdown of PAR-3 by small interfering RNA (siRNA) impaired cell migration, front-rear polarization, and PAR-3-mediated Rac1 activation, which were recovered with siRNA-resistant PAR-3, but not with the phospho-mimic PAR-3 mutant. We propose that RhoA/Rho-kinase inhibits PAR complex formation through PAR-3 phosphorylation, resulting in Rac1 inactivation.
In 2003, Japan's Ministry of Health, Labour and Welfare halted the neuroblastoma (NB) mass screening program, running since 1985. This study aimed to examine whether NB incidence and mortality changed before and after the program halted. This is a descriptive population-based study. We used data from the Monitoring of Cancer Incidence in Japan (MCIJ) project, Vital Statistics of Japan, and Japanese CANcer Survival Information for Society (J-CANSIS). Incidence rate, cumulative incidence rate, mortality rate, cumulative mortality rate, and relative 5-year survival for NB were calculated. Children were divided into two birth cohort groups, consisting of children born before, or after the cessation of the NB mass screening program. We compared the two cohorts, with regards to the cumulative incidence and mortality rates at 5 years old. The incidence rate was lower after the cessation of the NB mass screening program. There was no substantial change in the mortality rate, and no significant variation in the relative 5-year survival between groups. The cumulative incidence rate in the latter cohort was significantly lower than that in the former cohort (rate ratio: 0.39, 95% CI: 0.25-0.61, p < 0.001). No significant difference in the cumulative mortality rate between the two cohorts was observed (rate ratio: 0.99, 95% CI: 0.80-1.22, p = 0.93). The NB incidence rate decreased markedly and the mortality rate did not substantially change after the cessation of the NB mass screening program. The NB mass screening program probably caused overdiagnosis, and its effectiveness was not clear.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.