TFEB-dependent autophagy is involved in scavenger receptor OLR1/LOX-1-mediated tumor progression

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.