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
Affiliations
Soon Sang Park
Department of Biochemistry and Molecular Biology, Ajou University School of Medicine, Suwon 16499, Korea; Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon 16499, Korea; Inflamm-Aging Translational Research Center, Ajou University Medical Center, Suwon 16499, Korea
Young-Kyoung Lee
Department of Biochemistry and Molecular Biology, Ajou University School of Medicine, Suwon 16499, Korea; Inflamm-Aging Translational Research Center, Ajou University Medical Center, Suwon 16499, Korea
Yong Won Choi
Inflamm-Aging Translational Research Center, Ajou University Medical Center, Suwon 16499, Korea; Department of Hematology and Oncology, Ajou University School of Medicine, Suwon 16499, Korea
Su Bin Lim
Department of Biochemistry and Molecular Biology, Ajou University School of Medicine, Suwon 16499, Korea; Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon 16499, Korea; Inflamm-Aging Translational Research Center, Ajou University Medical Center, Suwon 16499, Korea
So Hyun Park
Inflamm-Aging Translational Research Center, Ajou University Medical Center, Suwon 16499, Korea; Department of Pathology, Ajou University School of Medicine, Suwon 16499, Korea
Han Ki Kim
Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon 16499, Korea; Department of Brain Science and Neurology, Ajou University School of Medicine, Suwon 16499, Korea
Jun Sang Shin
Department of Surgery, Ajou University School of Medicine, Suwon 16499, Korea
Young Hwa Kim
Inflamm-Aging Translational Research Center, Ajou University Medical Center, Suwon 16499, Korea; Department of Pathology, Ajou University School of Medicine, Suwon 16499, Korea
Dong Hyun Lee
Department of Biochemistry and Molecular Biology, Ajou University School of Medicine, Suwon 16499, Korea; Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon 16499, Korea; Inflamm-Aging Translational Research Center, Ajou University Medical Center, Suwon 16499, Korea
Jang-Hee Kim
Inflamm-Aging Translational Research Center, Ajou University Medical Center, Suwon 16499, Korea; Department of Pathology, Ajou University School of Medicine, Suwon 16499, Korea; Corresponding author
Tae Jun Park
Department of Biochemistry and Molecular Biology, Ajou University School of Medicine, Suwon 16499, Korea; Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon 16499, Korea; Inflamm-Aging Translational Research Center, Ajou University Medical Center, Suwon 16499, Korea; Corresponding author
Summary: 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.
