In the present review, we will present the molecular mechanisms behind the control p62 exerts over these pathways, their interconnection and how their deregulation contributes to cancer progression.
The concerted metabolic reprogramming across cancer and normal cellular compartments of the tumor microenvironment can favor tumorigenesis by increasing the survival and proliferating capacities of transformed cells. p62 has emerged as a critical signaling adaptor, beyond its role in autophagy, by playing an intricate context-dependent role in metabolic reprogramming of the cell types of the tumor and stroma, which shapes the tumor microenvironment to control tumor progression.
These findings expand our understanding of UVA-induced skin tumorigenesis and tumor progression and suggest that targeting p62 can help prevent or treat UVA-associated skin cancer.
We show that accumulation of the autophagy substrate p62/SQSTM1 in stressed Kras<sup>G12D</sup> acinar cells is associated with PDAC development and maintenance of malignancy in human cells and mice. p62 accumulation promotes neoplastic progression by controlling the NRF2-mediated induction of MDM2, which acts through p53-dependent and -independent mechanisms to abrogate checkpoints that prevent conversion of differentiated acinar cells to proliferative ductal progenitors.