Abstract 6801: Cellular senescence involves spatial evolution in colorectal cancer

Abstract Cancer evolution is a continuous process involving cellular changes that promote progression and metastasis. Recent studies demonstrate that cancer evolution is spatially associated: a phenomenon called “the spatial evolution of cancer.” In our data, colorectal cancer cells gradually evolve from an adenoid to a collective invasion morphology, ultimately developing a partial epithelial-mesenchymal transition phenotype as they form an invasive front. Trajectory analysis showed that cancer cells at the invasive front of a tumor exhibit a totally different gene expression pattern from those at the center, and that cellular senescence plays a crucial role in this transition. Epigenetic changes in the promoter/exon1 region of the CDKN2A gene caused by increased reactive oxygen species level are crucial for expression of p16INK4A and induction of senescence in the cancer cells. Two types of senescent tumor cells (type I and type II) were observed, and they played different roles in cancer progression due to different gene expression. Type II senescent tumor cells (p16INK4A+/LAMC2+/MMP7+), a final evolved form of cancer cells, are strongly associated with local invasion and lymph node metastasis of colorectal cancer and worsen the prognosis for patients. Citation Format: Tae Jun Park, Seok Yun Kang, Jang Hee Kim, Hyun Woo Lee, Yong Won Choi, Soon Sang Park, Young-Kyoung Lee. Cellular senescence involves spatial evolution in colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6801.