Autophagy at the crossroads of metabolism, stemness, and immunity in cancer progression
Year: 2026
Type: article
Abstract: Autophagy is a highly conserved cellular recycling process essential for maintaining homeostasis and responding to metabolic imbalance. In malignancy, this lysosome-dependent pathway is rewired by a complex network of oncogenic signaling pathways, including PI3K/Akt/mTOR, AMPK, and RAS/MAPK, which dictate cellular fitness under stress. This review explores the critical intersections where autophagy drives cancer progression by supporting metabolic adaptation, cancer stem cell (CSC) maintenance, and immune evasion. We highlight the functional repertoire of selective autophagy receptors—spanning ubiquitin-binding adaptors (such as p62/SQSTM1 and its non-canonical KEAP1–NRF2 signaling axis), hypoxia-induced mitophagy receptors (BNIP3, NIX, FUNDC1), and ER-phagy regulators (FAM134B, SEC62)—and examine how autophagic flux modulates the tumor microenvironment through macrophage recruitment and polarization. By synthesizing these three axes—metabolism, stemness, and immunity—we evaluate the therapeutic potential of targeting autophagy to overcome resistance and enhance modern cancer treatments.
Source: Frontiers in Immunology
Authors: Gaurav Shoeran, Namrata Anand
Institutions: University of Minnesota, University of Chicago
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7225741610