Extracellular matrix stiffness reduces DNA 6 ma level to facilitate colorectal cancer progression via disrupting P53 binding to CDKN1A promoter.

ABSTRACT: The extracellular matrix (ECM) forms the primary scaffold of the tumor microenvironment, with matrix stiffness serving as a critical physical cue that modulates cancer progression. However, the impact of matrix stiffness on colorectal cancer (CRC) progression remains elusive. This study aimed to elucidate the role of substrate stiffness in regulating DNA N6-methyladenine (6 mA) modifications and their association with CRC progression. We observed significantly reduced DNA 6 mA levels in CRC cells and tissues compared to normal controls, which progressively declined with advancing CRC stages. A negative correlation was identified between CRC tissue stiffness and DNA 6 mA levels. The 6 mA demethylase ALKBH1 was identified as a poor prognostic indicator in CRC and responded to increased subst

SUBMITTER: Xie SA 

PROVIDER: S-EPMC12382035 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature