RESUMO
Regulation of cellular actin dynamics is pivotal in driving cell motility. During cancer development, cells migrate to invade and spread; therefore, dysregulation of actin regulators is often associated with cancer progression. Here we report the role of ABRACL, a human homolog of the Dictyostelium actin regulator Costars, in migration and tumorigenic growth of cancer cells. We found a correlation between ABRACL expression and the migratory ability of cancer cells. Cell staining revealed the colocalization of ABRACL and F-actin signals at the leading edge of migrating cells. Analysis of the relative F-/G-actin contents in cells lacking or overexpressing ABRACL suggested that ABRACL promotes cellular actin distribution to the polymerized fraction. Physical interaction between ABRACL and cofilin was supported by immunofluorescence staining and proximity ligation. Additionally, ABRACL hindered cofilin-simulated pyrene F-actin fluorescence decay in vitro, indicating a functional interplay. Lastly, analysis on a colorectal cancer cohort demonstrated that high ABRACL expression was associated with distant metastasis, and further exploration showed that depletion of ABRACL expression in colon cancer cells resulted in reduced cell proliferation and tumorigenic growth. Together, results suggest that ABRACL modulates actin dynamics through its interaction with cofilin and thereby regulates cancer cell migration and participates in cancer pathogenesis.
Assuntos
Actinas/metabolismo , Carcinogênese/metabolismo , Carcinogênese/patologia , Movimento Celular , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Citoesqueleto de Actina/metabolismo , Fatores de Despolimerização de Actina/metabolismo , Idoso , Linhagem Celular Tumoral , Proliferação de Células , Forma Celular , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polimerização , Ligação ProteicaRESUMO
BACKGROUND: Eight infections occurred after modified radical mastectomies in a tertiary-care hospital. Group A streptococci (GAS) were isolated from three of the eight patients. METHODS: To control the outbreak, an epidemiologic investigation was conducted, and healthcare workers were screened for pathogens. Strains isolated from healthcare workers were compared with patient strains by emm typing. RESULTS: One surgeon attended one of the eight operations and observed the other seven. Streptococcus strains from the hands of this surgeon were identical to the patient strains. After the surgeon was suspended from duty and underwent eradication treatment, the outbreak was controlled. CONCLUSIONS: This outbreak of GAS infection is believed to have occurred by airborne transmission. Suspending patient care by healthcare workers who carry the causative GAS in a site(s) other than the respiratory tract for only the first 24 h they are receiving chemoprophylaxis may not be long enough. Sampling of the hands of healthcare workers during an investigation of nosocomial GAS infection is valuable.
