p15INK4B is an alternative marker of senescent tumor cells in colorectal cancer
Soon Sang Park,
Young-Kyoung Lee,
So Hyun Park,
Su Bin Lim,
Yong Won Choi,
Jun Sang Shin,
Young Hwa Kim,
Jang-Hee Kim,
Tae Jun Park
Affiliations
Soon Sang Park
Department of Biochemistry and Molecular Biology, Ajou University School of Medicine, Suwon, 16499, South Korea; Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon, 16499, South Korea; Inflamm-Aging Translational Research Center, Ajou University Medical Center, Suwon, 16499, South Korea
Young-Kyoung Lee
Department of Biochemistry and Molecular Biology, Ajou University School of Medicine, Suwon, 16499, South Korea; Inflamm-Aging Translational Research Center, Ajou University Medical Center, Suwon, 16499, South Korea
So Hyun Park
Inflamm-Aging Translational Research Center, Ajou University Medical Center, Suwon, 16499, South Korea; Department of Pathology, Ajou University School of Medicine, Suwon, 16499, South Korea
Su Bin Lim
Department of Biochemistry and Molecular Biology, Ajou University School of Medicine, Suwon, 16499, South Korea; Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon, 16499, South Korea; Inflamm-Aging Translational Research Center, Ajou University Medical Center, Suwon, 16499, South Korea
Yong Won Choi
Inflamm-Aging Translational Research Center, Ajou University Medical Center, Suwon, 16499, South Korea; Department of Hematology and Oncology, Ajou University School of Medicine, Suwon, 16499, South Korea
Jun Sang Shin
Department of Surgery, Ajou University School of Medicine, Suwon, 16499, South Korea
Young Hwa Kim
Inflamm-Aging Translational Research Center, Ajou University Medical Center, Suwon, 16499, South Korea
Jang-Hee Kim
Inflamm-Aging Translational Research Center, Ajou University Medical Center, Suwon, 16499, South Korea; Department of Pathology, Ajou University School of Medicine, Suwon, 16499, South Korea; Corresponding author. Department of Pathology, Ajou University School of Medicine, Suwon, 16499 South Korea.
Tae Jun Park
Department of Biochemistry and Molecular Biology, Ajou University School of Medicine, Suwon, 16499, South Korea; Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon, 16499, South Korea; Inflamm-Aging Translational Research Center, Ajou University Medical Center, Suwon, 16499, South Korea; Corresponding author. Department of Biochemistry and Molecular Biology, Ajou University School of Medicine, Suwon, 16499 South Korea.
Senescent tumor cells are nonproliferating tumor cells which are closely related to cancer progression by secreting senescence-related molecules, called senescence-associated secreting phenotypes. Therefore, the presence of senescent tumor cells is considered a prognostic factor in various cancer types. Although senescence-associated β-galactosidase staining is considered the best marker for detection of senescent tumor cells, it can only be performed in fresh-frozen tissues. p16INK4A, a cyclin-dependent inhibitor, has been used as an alternative marker to detect senescent tumor cells in formalin-fixed paraffin-embedded tissues. However, other reliable markers to detect senescent tumor cells is still lacking. In the present study, using public single-cell RNA-sequencing data, we found that p15INK4B, a cyclin-dependent kinase inhibitor, is a novel marker for detection of senescent tumor cells. Moreover, p15INK4B expression was positively correlated with that of p16INK4A in colorectal cancer tissues. In in vitro studies, mRNA expression of p15INK4B was increased together with that of p16INK4A in H2O2- and therapy-induced cancer senescence models. However, the mRNA level of p15INK4B did not increase in the oncogene-induced senescence model in primary colonic epithelial cells. In conclusion, p15INK4B is a potential alternative marker for detection of senescent tumor cells together with conventional markers in advanced stages of colorectal cancer.
