Frequent loss of metastatic ability in subclones of Apc, Kras, Tgfbr2, and Trp53 mutant intestinal tumor organoids.

ABSTRACT: Cancer evolution is explained by the accumulation of driver mutations and subsequent positive selection by acquired growth advantages, like Darwin's evolution theory. However, whether the negative selection of cells that have lost malignant properties contributes to cancer progression has not yet been fully investigated. Using intestinal metastatic tumor-derived organoids carrying Apc, Kras, Tgfbr2, and Trp53 quadruple mutations, we demonstrate here that approximately 30% of subclones of the organoids show loss of metastatic ability to the liver while keeping the driver mutations and oncogenic pathways. Notably, highly metastatic subclones also showed a gradual loss of metastatic ability during further passages. Such non-metastatic subclones revealed significantly decreased survival and pr

SUBMITTER: Morita A 

PROVIDER: S-EPMC10067385 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature