TFEB-dependent autophagy is involved in scavenger receptor OLR1/LOX-1-mediated tumor progression
TFEB-dependent autophagy is involved in scavenger receptor OLR1/LOX-1-mediated tumor progression
复制标题
TFEB 依赖性自噬参与清道夫受体 OLR1/LOX-1 介导的肿瘤进展。
DOI：
10.1080/15548627.2021.2012970
复制
发表时间：
2021-12-22
期刊：
影响因子：
13.3
通讯作者：
Wang, Lan
中科院分区：
文献类型：
--
作者：
Li, Can;Wang, Lan
巨自噬/自噬是一种进化上保守的分解代谢途径，需要维持细胞内环境的稳定。在癌症中，自噬的肿瘤细胞内在效应具有高度的上下文特异性，它可以促进癌细胞存活或诱导细胞程序性死亡。在这里，我们揭示了OLR1/LOX-1(氧化低密度脂蛋白受体1)是一种在食道癌细胞中高表达的清道夫受体，它通过抑制自噬细胞的死亡而参与肿瘤的发生。在机制上，OLR1与RACK1结合激活MAP2K/MEK-MAPK/ERK信号，导致转录因子EB(转录因子EB)被困在细胞核外，从而抑制自噬。此外，我们确定了一种导致OLR1降解的多糖，并抑制了这一自噬途径，以抑制肿瘤的发生。这项研究展示了自噬抑制肿瘤作用的新的分子机制，并为食道癌的治疗提供了见解。
Macroautophagy/autophagy is an evolutionarily conserved catabolic pathway required to maintain cellular homeostasis. In cancer, the tumor cell-intrinsic effects of autophagy are highly context specific, which could promote cancer cell survival or induce programmed cell death. Here, we reveal that OLR1/LOX-1 (oxidized low density lipoprotein receptor 1), a scavenger receptor highly expressed in esophageal cancer cells, is involved in tumorigenesis by suppressing autophagic cell death. Mechanistically, OLR1 binding to RACK1 activates MAP2K/MEK-MAPK/ERK signaling leading to TFEB (transcription factor EB) being trapped outside the nucleus and inhibiting autophagy. In addition, we identify a polysaccharide which causes the degradation of OLR1 and suppresses this autophagic pathway to inhibit tumorigenesis. This study demonstrates novel molecular mechanisms underlying the tumor-suppressive effect of autophagy and provides therapeutic insight for esophageal cancer.