Cellular senescence is associated with the spatial evolution toward a higher metastatic phenotype in colorectal cancer

• Published in: Cell reports (Cambridge) 2024-03, Vol.43 (3), p.113912-113912, Article 113912
• Main Authors: Park, Soon Sang, Lee, Young-Kyoung, Choi, Yong Won, Lim, Su Bin, Park, So Hyun, Kim, Han Ki, Shin, Jun Sang, Kim, Young Hwa, Lee, Dong Hyun, Kim, Jang-Hee, Park, Tae Jun
• Format: Article
• Language: English
• Subjects: cancer buddings; cancer evolution; Cellular Senescence - genetics; collective invasion; colorectal cancer; Colorectal Neoplasms - genetics; Colorectal Neoplasms - pathology; CP: Cancer; Cyclin-Dependent Kinase Inhibitor p16 - metabolism; Humans; LAMC2; lymph node metastasis; Matrix Metalloproteinase 7 - genetics; MMP7; Phenotype; senescent tumor cells; spatial evolution; spatial transcriptomics
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2024.113912

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 (p16INK4A+/CXCL12+/LAMC2−/MMP7−) are identified in the collective invasion region, whereas type II senescent tumor cells (p16INK4A+/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. [Display omitted] •Cellular senescence is associated with gradual phenotypic transition of cancer cells•Evolutionary path of cancer cells includes two types (I and II) of senescent tumor cells•Type II senescent tumor cells express MMP7 and are associated with higher metastatic potency Park et al. unravel the spatial heterogeneity of colorectal cancer and gradual phenotypic transition from the center to the invasive front. They demonstrated that cellular senescence is associated with this evolutional transition. Type II senescent tumor cells (p16INK4A+/LAMC2+/MMP7+) were found in the invasive front and are associated with higher metastatic potency.