Colorectal Cancer Cells-Derived Exosomal PIK3CA Mutation DNA Promotes Tumor Metastasis by Activating Fibroblast and Affecting Tumor Metastatic Microenvironment.

ABSTRACT: Exosomes participate in the formation of the tumor metastatic microenvironment (TME) by delivering tumor-specific substances. However, current studies mostly focus on exosomal RNA and proteins and lack an in-depth exploration of exosomal DNA. It is discovered that PIK3CA^H1047R mutant DNA in colorectal cancer (CRC) cell-derived exosomes can be delivered into recipient fibroblasts, where they are transcribed and translated, ultimately leading to the activation of fibroblasts into cancer-associated fibroblasts (CAFs) through interaction with the endogenous P85 regulatory subunit of the phosphatidylinositol 3-kinase (PI3K) pathway. CAFs have facilitated tumor cell migration in vitro and promote lung metastasis in vivo by secreting elevated levels of IL6. Additionally, the PIK3CA

SUBMITTER: Wang R 

PROVIDER: S-EPMC12279234 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature