Knockdown of the α5 laminin chain affects differentiation of colorectal cancer cells and their sensitivity to chemotherapy

The interaction of tumor cells with the extracellular matrix (ECM) may affect the rate of cancer progression and metastasis. One of the major components of ECM are laminins, the heterotrimeric glycoproteins consisting of α-, β-, and γ-chains (αβγ). Laminins interact with their cell surface receptors and, thus, regulate multiple cellular processes. In this work, we demonstrate that shRNA-mediated knockdown of the α5 laminin chain results in Wnt- and mTORC1-dependent partial dedifferentiation of colorectal cancer cells. Furthermore, we showed that this dedifferentiation involved activation of ER-stress signaling, pathway promoting the sensitivity of cells to 5-fluorouracil. [Display omitted] •Knockdown of the α5 laminin chain induced partial dedifferentiation of HT29 cells.•Dedifferentiation of HT29 cells was due to Wnt and mTORC1 signaling changes.•Knockdown of the α5 laminin chain was associated with ER-stress activation.•ER-stress facilitated sensitivity of HT29 cells to 5-fluorouracil.