RESUMEN
Cancerous cells are detrimental to the human body and can be incredibly resilient against treatments because of the complexities of molecular carcinogenic pathways. In particular, cancer cells are able to sustain increased growth under metabolic stress due to phenomena like the Warburg effect. Krüppel-like factor 4 (KLF4), a context-dependent transcription factor that can act as both a tumor suppressor and an oncogene, is involved in many molecular pathways that respond to low glucose and increased reactive oxygen species (ROS), raising the question of its role in metabolic stress as a result of increased proliferation of tumor cells. In this study, metabolic assays were performed, showing enhanced efficiency of energy production in cells expressing KLF4. Western blotting showed that KLF4 increases the expression of essential glycolytic proteins. Furthermore, we used immunostaining to show that KLF4 increases the localization of glucose transporter 1 (GLUT1) to the cellular membrane. 2',7'-Dichlorodihydrofluorescein diacetate (H2DCF-DA) was used to analyze the production of ROS, and we found that KLF4 reduces stress-induced ROS within cells. Finally, we demonstrated increased autophagic death in KLF4-expressing cells in response to glucose starvation. Collectively, these results relate KLF4 to non-Warburg metabolic behaviors that support its role as a tumor suppressor and could make KLF4 a target for new cancer treatments.
Asunto(s)
Homeostasis , Factores de Transcripción de Tipo Kruppel/metabolismo , Estrés Fisiológico , Animales , Autofagia , Membrana Celular/metabolismo , Metabolismo Energético/genética , Regulación de la Expresión Génica , Glucosa/deficiencia , Transportador de Glucosa de Tipo 1/metabolismo , Glucólisis/genética , Factor 4 Similar a Kruppel , Factores de Transcripción de Tipo Kruppel/genética , Ratones Endogámicos C57BL , Modelos Biológicos , Especies Reactivas de Oxígeno/metabolismo , Estrés Fisiológico/genéticaRESUMEN
BACKGROUND/AIM: As the population ages, older adults are being encouraged through policy to remain living in their home and community. Occupational therapists are in a position to support individuals to engage in meaningful occupations, acknowledging the influence of personal and environmental factors on community participation. The purpose of this study was to understand the meaning and experience of community for older Australian adults. METHODS: A cross-sectional phenomenological research study design was utilised. Convenience and snowball sampling were used to recruit 32 participants with ages ranging from 65 to 94 years living in the south east region of Queensland, Australia. Semi-structured interviews were conducted and thematic analysis was used to explore the participants' responses. RESULTS: Four final themes were revealed: organised things in the community, community is people, community is what you make of it and the meaning of community is life. CONCLUSION: The results support that community extends beyond physicality, with personal motivation, the social environment and community involvement identified as important constructs within each of the themes. The findings provide a foundation for future research and occupational therapy practices to support older adults to age in place.