Cell adhesion molecule IGPR-1 activates AMPK connecting cell adhesion to autophagy.

Autophagy plays critical roles in the maintenance of endothelial cells in response to cellular stress caused by blood flow. There is growing evidence that both cell adhesion and cell detachment can modulate autophagy, but the mechanisms responsible for this regulation remain unclear. Immunoglobulin and proline-rich receptor-1 (IGPR-1) is a cell adhesion molecule that regulates angiogenesis and endothelial barrier function. In this study, using various biochemical and cellular assays, we demonstrate that IGPR-1 is activated by autophagy-inducing stimuli, such as amino acid starvation, nutrient deprivation, rapamycin, and lipopolysaccharide. Manipulating the IκB kinase ß activity coupled with in vivo and in vitro kinase assays demonstrated that IκB kinase ß is a key serine/threonine kinase activated by autophagy stimuli and that it catalyzes phosphorylation of IGPR-1 at Ser220 The subsequent activation of IGPR-1, in turn, stimulates phosphorylation of AMP-activated protein kinase, which leads to phosphorylation of the major pro-autophagy proteins ULK1 and Beclin-1 (BECN1), increased LC3-II levels, and accumulation of LC3 punctum. Thus, our data demonstrate that IGPR-1 is activated by autophagy-inducing stimuli and in response regulates autophagy, connecting cell adhesion to autophagy. These findings may have important significance for autophagy-driven pathologies such cardiovascular diseases and cancer and suggest that IGPR-1 may serve as a promising therapeutic target.

Geographic Barriers Affect Follow-Up Care in Head and Neck Cancer.

OBJECTIVES/HYPOTHESIS: Follow-up care in head and neck cancers (HNC) is critical in managing patient health. However, social determinants of health (SDOH) can create difficulties in maintaining follow-up care. The study goal is to explore how SDOH impacts maintenance of HNC follow-up care appointments. METHODS: A systematic retrospective chart review of 877 HNC patients diagnosed in the past 10 years a safety-net tertiary care hospital with systems to help reduce care disparities. Cohort groups were identified and compared against protocols for follow-up. Data were analyzed using analysis of variance, chi-square tests, Fisher's exact tests, two-sample t-tests, and simple linear regression. RESULTS: The average length of follow-up time in months and average total number of follow-ups over 5 years were 32.96 (34.60) and 9.24 (7.87), respectively. There was no significant difference in follow-up care between United States (US) versus non-US born and English versus non-English speaking patients. Race/ethnicity, county median household income, insurance status, and county educational attainment were not associated with differences in follow-up. However, living a greater distance from the hospital was associated with lower follow-up length and less frequency in follow-up (P < .0001). CONCLUSION: While income, primary language, country of birth, race/ethnicity, insurance status, and markers of educational attainment do not appear to impact HNC follow-up at our safety-net, tertiary care institution, and distance from hospital remains an important contributor to disparities in care. This study shows that many barriers to care can be addressed in a model that addresses SDOH, but there are barriers that still require additional systems and resources. Laryngoscope, 132:1022-1028, 2022.

Social determinants of health and treatment decisions in head and neck cancer.

BACKGROUND: This study compares select social determinants of health (SDOH) with treatment modality selection and treatment completion in head and neck cancer (HNC) patients, to better understand disparities in health outcomes. METHODS: A retrospective cohort study of HNC (n = 1428) patients was conducted. Demographic and disease-specific variables were recorded, including treatment modality selection and completion. Data were analyzed using two-sample t tests, chi-square, and Fisher's exact tests. RESULTS: Primary language was significantly associated with treatment choice, where non-English speakers were less likely to choose treatment as recommended by the Tumor Board. Lower mean distance from the hospital (37.38 [48.31] vs. 16.92 [19.10], p < 0.0001) and a county-based higher mean percentage of bachelor degree or higher education (42.16 [8.82] vs. 44.95 [6.19], p < 0.0003) were associated with treatment selection. CONCLUSION: Language, distance from the hospital, and education affected treatment selection in this study and may be useful in understanding how to counsel patients on treatment selection for HNC.