Cellular senescence is associated with the spatial evolution toward a higher metastatic phenotype in colorectal cancer
Soon Sang Park, Young‐Kyoung Lee, Yong Won Choi, Su Bin Lim, So Hyun Park, Han Ki Kim, Jun Sang Shin, Young Hwa Kim, Dong Hyun Lee, Jang‐Hee Kim, Tae Jun Park
Abstract
In this study, we explore the dynamic process of colorectal cancer progression, emphasizing the evolution toward a more metastatic phenotype. The term "evolution" as used in this study specifically denotes the phenotypic transition toward a higher metastatic potency from well-formed glandular structures to collective invasion, ultimately resulting in the development of cancer cell buddings at the invasive front. Our findings highlight the spatial correlation of this evolution with tumor cell senescence, revealing distinct types of senescent tumor cells (types I and II) that play different roles in the overall cancer progression. Type I senescent tumor cells (p16 INK4A+ /CXCL12 + /LAMC2 − /MMP7 − ) are identified in the collective invasion region, whereas type II senescent tumor cells (p16 INK4A+ /CXCL12 + /LAMC2 + /MMP7 + ), representing the final evolved form, are prominently located in the partial-EMT region. Importantly, type II senescent tumor cells associate with local invasion and lymph node metastasis in colorectal cancer, potentially affecting patient prognosis.