A new mechanism has been discovered that causes the “basal” subtype of pancreatic cancer, a malignant type with a particularly poor prognosis.
The research team of Professor Lee Da-geun (Research Professor Jae-il Choi) from the Department of Pathology and Professors Yu-seon Kim and Su-bin Lim from the Department of Biochemistry at Ajou Medical University found that the “subtype basal” ‘, a malignant type of pancreatic cancer, can be formed by tumor necrosis factor derived from macrophages around the cancer. It was announced on the 10th.
From left, Professor Lee Da-geun and Research Professor Jae-il Choi from the Department of Pathology, and Professor Yu-seon Kim and Soo-bin Lim from the Department of Biochemistry, Ajou University Faculty of Medicine.
The results of this study were published as an article in the recent online edition of the international journal Clinical and Translational Medicine.
According to him, pancreatic cancer, a representative incurable cancer, is divided into two molecular subtypes: “classic” and “baseline-like”. Among them, the basal subtype is known to be a malignant type that shows resistance to treatment and has a significantly higher patient mortality rate.
The research team discovered for the first time that the expression of TAp63, one of the isoforms of TP63, was increased in the basal subtype.
Furthermore, it was experimentally confirmed that a basal subtype can be formed simply by increasing TAp63 expression, and this was verified using TCGA (Cancer Genome Map) data.
Furthermore, activation of NF-κB by tumor necrosis factor in pancreatic cancer cells was confirmed to induce increased TAp63 expression. Furthermore, single cell sequencing (scRNA-seq) analysis revealed that the major source of these tumor necrosis factors is macrophages and that macrophage infiltration is significantly increased in the “baseline-like” subtype.
Professor Lee Da-geun, the corresponding author, said: “Contrary to the existing concept, we have once again demonstrated the importance of the tumor microenvironment by confirming that extracellular stimulation determines the molecular subtype of tumor cells.”
Professor Kim Yu-seon, co-corresponding author, said: “We hope that treatment targeting the ‘macrophage-tumor necrosis factor-basal-like’ axis, which forms the pancreatic cancer subtype, will help improve the performance of malignant tumor treatment. in the future the “basal-like” subtype. “I hope so,” he added.
This research was conducted with support from the Outstanding Younger Support Project of the National Research Foundation of Korea, the Creative Challenge Support Project, the Mid-career Researcher Support Project, and the Basic Research Lab (BRL).
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2024-01-10 03:39:11
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