A role of DDR2 and substrate stiffness on cancer cell transcriptome and proliferation

Extracellular matrix (ECM) regulates carcinogenesis. As a major ECM component, collagen interacts with integrin and a non-typical receptor discoidin domain receptor tyrosine kinase 2 (DDR2), but how DDR2 regulates cancer progression is poorly understood. Apart from its signaling function, ECM provides a mechanical environment for cancer, but the impact of biomechanics on cancer remains enigmatic. Here, we performed RNA-seq of a human neuroblastoma cell line SH-SY5Y. We found that DDR2 knockdown, but not increasing substrate stiffness, upregulated pro-proliferative genes and down-regulated axonogenesis genes. Surprisingly, despite no transcriptome changes, increasing of stiffness attenuates SH-SY5Y cell proliferation, an effect also observed after DDR2 knockdown. Our results indicate that two ECM effectors, DDR2 and biomechanics, could control cancer cell proliferation through different mechanisms. To investigate how DDR2 regulates cancer progresion, we did DDR2 knock down in SH-SY5Y cell line, then followed by RNA-seq.