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 (LPS). Manipulating the IκB kinaseβ (IKKβ) activity coupled with in vivo and in vitro kinase assays demonstrated that IKKb is a key serine/threonine kinase activated by autophagy stimuli and catalyzes phosphorylation of IGPR-1 at Ser220. The subsequent activation of IGPR-1, in turn, stimulates phosphorylation of AMP-activated protein kinase (AMPK), which leads to phosphorylation of 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.

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

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 twosample 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.

Cellular stress caused by loss of extracellular matrix (ECM)-cell interaction involving integrins induces autophagy and autophagy is considered to protect cells from anoikis (i.e., cell death due to loss of cell adhesion). Immunoglobulin (Ig) and proline-rich receptor-1 (IGPR-1) is a newly identified cell adhesion molecule that mediates cell-cell adhesion and supports cell survival in response to anoikis.However, whether IGPR-1 is activated in response to and mediates autophagy is not known. In this study, we demonstrate that IGPR-1 is activated by autophagy inducing stimuli, such as nutrient deprivation, rapamycin and lipopolysaccharide (LPS). We have identified IκB kinaseβ (IKKβ) as a key serine/threonine kinase activated by autophagy stimuli and mediates phosphorylation of IGPR-1 at Ser220. Activation of IGPR-1, in turn, stimulates phosphorylation of AMP-activated protein kinase (AMPK), which leads to phosphorylation of key pro-autophagy proteins, ULK1 and Beclin-1, increased LC3-II levels and accumulation of LC3 punctum. This study demonstrates that IGPR-1 is activated by and regulates autophagy, connecting cell adhesion to autophagy, a finding that has important significance for autophagy-driven pathologies such cardiovascular diseases and cancer. Introduction:Autophagy (also called macroautophagy), the lysosomal degradation of cytoplasmic organelles or cytosolic components, is an evolutionarily conserved cytoprotective mechanism that is induced in response to cellular stress, such as nutrient withdrawal, loss of cell adhesion, and flow shear stress, or by therapeutic genotoxic agents and others 1, 2 . Cell-extracellular matrix (ECM) adhesion through engagement of cell adhesion molecules (CAMs) (e.g., integrins) is thought to regulate autophagy 3, 4 and more importantly loss of cell adhesion to ECM is linked to induction of autophagy 4, 5 .Upon autophagy, unc-51-like kinase 1 (ULK1 also known as ATG1) associates with autophagy-related protein 13 (ATG13), and focal adhesion kinase family interacting protein of 200 kD (FIP200) to form the ULK1 complex. ULK1 interaction with ATG13 and FIP200 is critical for ULK1 kinase activity and stability 6 .The ULK1 complex translocates to autophagy initiation sites and recruits the class III phosphatidylinositol 3-kinase, vacuolar protein sorting 34 (VPS34) complex consisting of BECLIN-1 (the mammalian orthologue of the yeast autophagy protein Apg6/Vps30 7 and multiple other ATGs leading to the phagophore formation 8 . The serine/threonine protein kinase mTOR (mechanistic target of rapamycin) complex 1 (mTORC1) is a key regulator of autophagy in response to nutrient availability. In the presence of amino acids, mTORC1 is activated and suppresses autophagy through phosphorylation of ULK1 and ATG13. However, upon nutrient deprivation, mTORC1 activity is inhibited leading to the activation of ULK1 that induces the autophagy program 9, 10 . Suppression of mTORC1 activity by AMP-activated protein kinase (AMPK) is central to regulation of autophagy. AMPK inactivates mTORC1 throu...