AGE/RAGE axis regulates reversible transition to quiescent states of ALK-rearranged NSCLC and pancreatic cancer cells in monolayer cultures
Abstract Cancer recurrence due to tumor cell quiescence after therapy and long-term remission is associated with cancer-related death. Previous studies have used cell models that are unable to return to a proliferative state; thus, the transition between quiescent and proliferative states is not wel...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-06-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-14272-0 |
| _version_ | 1811242252116164608 |
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| author | Tetsuya Kadonosono Kotaro Miyamoto Shiori Sakai Yoshiyuki Matsuo Shojiro Kitajima Qiannan Wang Minori Endo Mizuho Niibori Takahiro Kuchimaru Tomoyoshi Soga Kiichi Hirota Shinae Kizaka-Kondoh |
| author_facet | Tetsuya Kadonosono Kotaro Miyamoto Shiori Sakai Yoshiyuki Matsuo Shojiro Kitajima Qiannan Wang Minori Endo Mizuho Niibori Takahiro Kuchimaru Tomoyoshi Soga Kiichi Hirota Shinae Kizaka-Kondoh |
| author_sort | Tetsuya Kadonosono |
| collection | DOAJ |
| description | Abstract Cancer recurrence due to tumor cell quiescence after therapy and long-term remission is associated with cancer-related death. Previous studies have used cell models that are unable to return to a proliferative state; thus, the transition between quiescent and proliferative states is not well understood. Here, we report monolayer cancer cell models wherein the human non-small cell lung carcinoma cell line H2228 and pancreatic cancer cell line AsPC-1 can be reversibly induced to a quiescent state under hypoxic and serum-starved (HSS) conditions. Transcriptome and metabolome dual-omics profiles of these cells were compared with those of the human lung adenocarcinoma cell line A549, which was unable to enter a quiescent state under HSS conditions. The quiescence-inducible cells had substantially lower intracellular pyruvate and ATP levels in the quiescent state than in the proliferative state, and their response to sudden demand for energy was dramatically reduced. Furthermore, in quiescence-inducible cells, the transition between quiescent and proliferative states of these cells was regulated by the balance between the proliferation-promoting Ras and Rap1 signaling and the suppressive AGE/RAGE signaling. These cell models elucidate the transition between quiescent and proliferative states, allowing the development of drug-screening systems for quiescent tumor cells. |
| first_indexed | 2024-04-12T13:48:59Z |
| format | Article |
| id | doaj.art-04df67d4e5dd44408996ce01414b499b |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-12T13:48:59Z |
| publishDate | 2022-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-04df67d4e5dd44408996ce01414b499b2022-12-22T03:30:35ZengNature PortfolioScientific Reports2045-23222022-06-0112111310.1038/s41598-022-14272-0AGE/RAGE axis regulates reversible transition to quiescent states of ALK-rearranged NSCLC and pancreatic cancer cells in monolayer culturesTetsuya Kadonosono0Kotaro Miyamoto1Shiori Sakai2Yoshiyuki Matsuo3Shojiro Kitajima4Qiannan Wang5Minori Endo6Mizuho Niibori7Takahiro Kuchimaru8Tomoyoshi Soga9Kiichi Hirota10Shinae Kizaka-Kondoh11School of Life Science and Technology, Tokyo Institute of TechnologySchool of Life Science and Technology, Tokyo Institute of TechnologySchool of Life Science and Technology, Tokyo Institute of TechnologyDepartment of Human Stress Response Science, Institute of Biomedical Science, Kansai Medical UniversityInstitute for Advanced Biosciences, Keio UniversitySchool of Life Science and Technology, Tokyo Institute of TechnologySchool of Life Science and Technology, Tokyo Institute of TechnologySchool of Life Science and Technology, Tokyo Institute of TechnologyCenter for Molecular Medicine, Jichi Medical UniversityInstitute for Advanced Biosciences, Keio UniversityDepartment of Human Stress Response Science, Institute of Biomedical Science, Kansai Medical UniversitySchool of Life Science and Technology, Tokyo Institute of TechnologyAbstract Cancer recurrence due to tumor cell quiescence after therapy and long-term remission is associated with cancer-related death. Previous studies have used cell models that are unable to return to a proliferative state; thus, the transition between quiescent and proliferative states is not well understood. Here, we report monolayer cancer cell models wherein the human non-small cell lung carcinoma cell line H2228 and pancreatic cancer cell line AsPC-1 can be reversibly induced to a quiescent state under hypoxic and serum-starved (HSS) conditions. Transcriptome and metabolome dual-omics profiles of these cells were compared with those of the human lung adenocarcinoma cell line A549, which was unable to enter a quiescent state under HSS conditions. The quiescence-inducible cells had substantially lower intracellular pyruvate and ATP levels in the quiescent state than in the proliferative state, and their response to sudden demand for energy was dramatically reduced. Furthermore, in quiescence-inducible cells, the transition between quiescent and proliferative states of these cells was regulated by the balance between the proliferation-promoting Ras and Rap1 signaling and the suppressive AGE/RAGE signaling. These cell models elucidate the transition between quiescent and proliferative states, allowing the development of drug-screening systems for quiescent tumor cells.https://doi.org/10.1038/s41598-022-14272-0 |
| spellingShingle | Tetsuya Kadonosono Kotaro Miyamoto Shiori Sakai Yoshiyuki Matsuo Shojiro Kitajima Qiannan Wang Minori Endo Mizuho Niibori Takahiro Kuchimaru Tomoyoshi Soga Kiichi Hirota Shinae Kizaka-Kondoh AGE/RAGE axis regulates reversible transition to quiescent states of ALK-rearranged NSCLC and pancreatic cancer cells in monolayer cultures Scientific Reports |
| title | AGE/RAGE axis regulates reversible transition to quiescent states of ALK-rearranged NSCLC and pancreatic cancer cells in monolayer cultures |
| title_full | AGE/RAGE axis regulates reversible transition to quiescent states of ALK-rearranged NSCLC and pancreatic cancer cells in monolayer cultures |
| title_fullStr | AGE/RAGE axis regulates reversible transition to quiescent states of ALK-rearranged NSCLC and pancreatic cancer cells in monolayer cultures |
| title_full_unstemmed | AGE/RAGE axis regulates reversible transition to quiescent states of ALK-rearranged NSCLC and pancreatic cancer cells in monolayer cultures |
| title_short | AGE/RAGE axis regulates reversible transition to quiescent states of ALK-rearranged NSCLC and pancreatic cancer cells in monolayer cultures |
| title_sort | age rage axis regulates reversible transition to quiescent states of alk rearranged nsclc and pancreatic cancer cells in monolayer cultures |
| url | https://doi.org/10.1038/s41598-022-14272-0 |
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