Updated project metadata. HepaRG progenitor cells are liver carcinoma cells that exhibit transdifferentiation properties, however, the underlying mechanisms remain poorly known. To evaluate whether a compression stress that mimics the tumoral microenvironment can drive the transdifferentiation of HepaRG cells, we analysed their proteome after modulating the density at which they are grown (compression at high density) and their hormonal environment. We determined a molecular signature of the new HepaRG-derived cell lines, reflecting their differentiation status and stress- and chromatin-related responses. In addition to be a promising way of creating a variety of new cell lines for the study of, e.g., tumoral progression, physical constraint paves the way for the development of new solutions to improve the prognosis of cancer.