Intersections between Regulated Cell Death and Autophagy

Abstract

Mutations in Lef1 occur in human and mouse sebaceous gland (SG) tumors, but their contribution to carcinogenesis remains unclear. Since Gata6 controls lineage identity in SG, we investigated the link between these two transcription factors. Here, we show that Gata6 is a b-catenin-independent transcriptional target of mutant Lef1. During epidermal development, Gata6 is expressed in a subset of Sox9-positive Lef1-negative hair follicle progenitors that give rise to the upper SG. Overexpression of Gata6 by in utero lentiviral injection is sufficient to induce ectopic sebaceous gland elements. In mice overexpressing mutant Lef1, Gata6 ablation increases the total number of skin tumors yet decreases the proportion of SG tumors. The increased tumor burden correlates with impaired DNA mismatch repair and decreased expression of Mlh1 and Msh2 genes, defects frequently observed in human sebaceous neoplasia. Gata6 specifically marks human SG tumors and also defines tumors with elements of sebaceous differentiation, including a subset of basal cell carcinomas. Our findings reveal that Gata6 controls sebaceous gland development and cancer.

Molecular Response of Rabbit Menisci to Surgically Induced Hemarthrosis and a Single Intra‐Articular Dexamethasone Treatment

“…Second, we did not assess components of other cell death pathways to investigate whether more than one pathway may be involved in the observed cell death. This may be relevant as there are reports of intersections and cross‐talk between different pathways (reviewed in Napoletano et al and Song et al). Furthermore, in the in vitro studies, the menisci were cultured in the absence of mechanical loading, which has been reported to disrupt homeostasis of the medial meniscus differently than the lateral .…”

Cell death induced by the ER stressor thapsigargin involves death receptor 5, a non-autophagic function of MAP1LC3B, and distinct contributions from unfolded protein response components

“…the involvement of caspases and various Bcl-2 protein family members [5,74,75], the initiating events -and how the various components of the UPR integrate on them -are less well defined. Moreover, the role played by autophagy and ATG proteins, which are very often implicated in cell fate decisions [28], is uncertain. Numerous studies have shown that ER stress-induced cell death-initiation involves death receptor-associated activation of caspase-8 [9, 13, 17-22, 26, 27].…”

“…Autophagy and autophagy-related (ATG) proteins are frequently implicated in cell death regulation [28], but their role in ER stress-induced cell death is unclear. ER stress potently upregulates the expression of microtubuleassociated proteins 1A/1B light chain 3B (LC3B), as well as other ATGs [29][30][31][32][33].…”

11-Methoxytabersonine Induces Necroptosis with Autophagy through AMPK/mTOR and JNK Pathways in Human Lung Cancer Cells

“…Thus, autophagy is crucial for maintaining cellular homeostasis and plays a prosurvival role. 12,13) In other cases, autophagy can induce a prodeath signal pathway. 14) Therefore, autophaghy can determine cell fate.…”