Gene expression of KP4 and A549 cells regulated by matrix stiffness and ATF5

Cancer tissues are stiffer than normal tissues. Carcinogenesis stiffens the extracellular matrix (ECM) of cancerous tissues, to which cancer cells respond by activating transcription factors. We show that activating transcription factor 5 (ATF5), highly expressed in tumors, is activated by ECM stiffness and promotes the proliferation of cancer cells, including that of pancreatic cancer cells (KP4) and lung cancer cells (A549). In addition, ATF5 suppressed the expression of early growth response 1 (EGR1), thereby accelerating cancer cell proliferation. Stiff ECMs trigger the JAK-MYC pathway which activates ATF5. KP4 and A549 cells were cultured on stiff (collagen-coated plastic) or soft (collagen gel) matrices. These cells were also transfected with negative control (NC) RNA, siATF5-1, or siATF5-2 and cultured on stiff matrices.