Increased expression of TRPM8 and p21/Cip1 in epithelial carcinoma cells in confluent conditions
Based on that TRPM8 is a key factor of normal cell-carcinoma cell interaction and there is a tendency for proliferation of some cell types that are repressed in a high-density state rather than in a low-density state, we attempted to clarify the relationship between direct cell-cell interactions and...
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| Published in | Fundamental Toxicological Sciences Vol. 12; no. 1; pp. 17 - 20 |
|---|---|
| Main Author | |
| Format | Journal Article |
| Language | English |
| Published |
The Japanese Society of Toxicology
2025
一般社団法人 日本毒性学会 |
| Subjects | |
| Online Access | Get full text |
| ISSN | 2189-115X 2189-115X |
| DOI | 10.2131/fts.12.17 |
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| Abstract | Based on that TRPM8 is a key factor of normal cell-carcinoma cell interaction and there is a tendency for proliferation of some cell types that are repressed in a high-density state rather than in a low-density state, we attempted to clarify the relationship between direct cell-cell interactions and expression of TRPM8, repressor of carcinoma cell proliferation. We examined TRPM8 and p21/Cip1 levels in normal and carcinoma epithelial cells at low and high cell density (confluent). TRPM8 and p21/Cip1 levels in confluent carcinoma cells markedly increased as compared with that of carcinoma cells in low density and normal cells in low density and confluent. When carcinoma cells cultured to confluent were re-seeded at low density, TRPM8 and p21/Cip1 levels decreased, indicating that the direct cell-cell interaction may regulate the expression of TRPM8 and p21/Cip1 in carcinoma cells. Totally, TRPM8 functions as repressor of cell proliferation in the condition which enables direct interaction between carcinoma cells occurs. |
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| AbstractList | Based on that TRPM8 is a key factor of normal cell-carcinoma cell interaction and there is a tendency for proliferation of some cell types that are repressed in a high-density state rather than in a low-density state, we attempted to clarify the relationship between direct cell-cell interactions and expression of TRPM8, repressor of carcinoma cell proliferation. We examined TRPM8 and p21/Cip1 levels in normal and carcinoma epithelial cells at low and high cell density (confluent). TRPM8 and p21/Cip1 levels in confluent carcinoma cells markedly increased as compared with that of carcinoma cells in low density and normal cells in low density and confluent. When carcinoma cells cultured to confluent were re-seeded at low density, TRPM8 and p21/Cip1 levels decreased, indicating that the direct cell-cell interaction may regulate the expression of TRPM8 and p21/Cip1 in carcinoma cells. Totally, TRPM8 functions as repressor of cell proliferation in the condition which enables direct interaction between carcinoma cells occurs. |
| Author | Fujino, Tomofumi |
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| Cites_doi | 10.2131/jts.47.117 10.2131/fts.11.11 10.1083/jcb.106.3.761 10.3390/ijms20235972 10.2131/fts.10.1 10.1073/pnas.0910009106 10.1016/S0092-8674(02)00652-9 10.3390/ani10071174 |
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| References | Peier, A.M., Moqrich, A., Hergarden, A.C., Reeve, A.J., Andersson, D.A., Story, G.M., Earley, T.J., Dragoni, I., McIntyre, P., Bevan, S. and Patapoutian, A. (2002): A TRP channel that senses cold stimuli and menthol. Cell, 108, 705-715. Takahashi, K., Kanazawa, H., Akiyama, Y., Tazaki, S., Takahara, M., Muto, T., Tanzawa, H. and Sato, K. (1989): Establishment and characterization of a cell line (SAS) from poorly differentiated human squamous cell carcinoma of the tongue. J. Jpn. Stomatol. Soc., 38, 20-28. Díaz-Coránguez, M., Liu, X. and Antonetti, D.A. (2019): Tight Junctions in Cell Proliferation. Int. J. Mol. Sci., 20, 5972-6001. Fujino, T. (2022): Transient Receptor Potential Melastatin 8, a sensor of cold temperatures mediates expression of cyclin-dependent kinase inhibitor, p21/Cip1, a regulator of epidermal cell proliferation. J. Toxicol. Sci., 47, 117-123. Liu, M., Casimiro, M.C., Wang, C., Shirley, L.A., Jiao, X., Katiyar, S., Ju, X., Li, Z., Yu, Z., Zhou, J., Johnson, M., Fortina, P., Hyslop, T., Windle, J.J. and Pestell, R.G. (2009): p21CIP1 attenuates Ras- and c-Myc-dependent breast tumor epithelial mesenchymal transition and cancer stem cell-like gene expression in vivo. Proc. Natl. Acad. Sci. USA, 106, 19035-19039. Islam, M.A., Mizusawa, M., Sharmin, M.M., Hayashi, S. and Yonekura, S. (2020): TRPV4 Increases the Expression of Tight Junction Protein-Encoding Genes via XBP1 in Mammary Epithelial Cells. Animals (Basel), 10, 1174-1185. Fujino, T. and Ohkawa, S. (2024): Indeterminate alteration of TRPM8 and p21/Cip1 levels in normal human keratinocytes by incubating with medium including substances released by squamous carcinoma cells Fund. Toxicol. Sci., 11, 11-15. Boukamp, P., Petrussevska, R.T., Breitkreutz, D., Hornung, J., Markham, A. and Fusenig, N.E. (1988): Normal keratinization in a spontaneously immortalized aneuploid human keratinocyte cell line. J. Cell Biol., 106, 761-771. Fujino, T., Nakamura, M. and Ohkawa, S. (2023): PPAR gamma negatively regulates the expression of TRPM8 in normal epidermal cells but mutually regulate their expressions with TRPM8 by feed-back loop regulation in squamous carcinoma cells. Fundam. Toxicol. Sci., 10, 1-6. 1 2 3 4 5 6 7 8 9 |
| References_xml | – reference: Boukamp, P., Petrussevska, R.T., Breitkreutz, D., Hornung, J., Markham, A. and Fusenig, N.E. (1988): Normal keratinization in a spontaneously immortalized aneuploid human keratinocyte cell line. J. Cell Biol., 106, 761-771. – reference: Fujino, T. and Ohkawa, S. (2024): Indeterminate alteration of TRPM8 and p21/Cip1 levels in normal human keratinocytes by incubating with medium including substances released by squamous carcinoma cells Fund. Toxicol. Sci., 11, 11-15. – reference: Peier, A.M., Moqrich, A., Hergarden, A.C., Reeve, A.J., Andersson, D.A., Story, G.M., Earley, T.J., Dragoni, I., McIntyre, P., Bevan, S. and Patapoutian, A. (2002): A TRP channel that senses cold stimuli and menthol. Cell, 108, 705-715. – reference: Takahashi, K., Kanazawa, H., Akiyama, Y., Tazaki, S., Takahara, M., Muto, T., Tanzawa, H. and Sato, K. (1989): Establishment and characterization of a cell line (SAS) from poorly differentiated human squamous cell carcinoma of the tongue. J. Jpn. Stomatol. Soc., 38, 20-28. – reference: Liu, M., Casimiro, M.C., Wang, C., Shirley, L.A., Jiao, X., Katiyar, S., Ju, X., Li, Z., Yu, Z., Zhou, J., Johnson, M., Fortina, P., Hyslop, T., Windle, J.J. and Pestell, R.G. (2009): p21CIP1 attenuates Ras- and c-Myc-dependent breast tumor epithelial mesenchymal transition and cancer stem cell-like gene expression in vivo. Proc. Natl. Acad. Sci. USA, 106, 19035-19039. – reference: Islam, M.A., Mizusawa, M., Sharmin, M.M., Hayashi, S. and Yonekura, S. (2020): TRPV4 Increases the Expression of Tight Junction Protein-Encoding Genes via XBP1 in Mammary Epithelial Cells. Animals (Basel), 10, 1174-1185. – reference: Fujino, T. (2022): Transient Receptor Potential Melastatin 8, a sensor of cold temperatures mediates expression of cyclin-dependent kinase inhibitor, p21/Cip1, a regulator of epidermal cell proliferation. J. Toxicol. Sci., 47, 117-123. – reference: Fujino, T., Nakamura, M. and Ohkawa, S. (2023): PPAR gamma negatively regulates the expression of TRPM8 in normal epidermal cells but mutually regulate their expressions with TRPM8 by feed-back loop regulation in squamous carcinoma cells. Fundam. Toxicol. Sci., 10, 1-6. – reference: Díaz-Coránguez, M., Liu, X. and Antonetti, D.A. (2019): Tight Junctions in Cell Proliferation. Int. J. Mol. Sci., 20, 5972-6001. – ident: 3 doi: 10.2131/jts.47.117 – ident: 5 doi: 10.2131/fts.11.11 – ident: 1 doi: 10.1083/jcb.106.3.761 – ident: 2 doi: 10.3390/ijms20235972 – ident: 4 doi: 10.2131/fts.10.1 – ident: 7 doi: 10.1073/pnas.0910009106 – ident: 8 doi: 10.1016/S0092-8674(02)00652-9 – ident: 9 – ident: 6 doi: 10.3390/ani10071174 |
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| Title | Increased expression of TRPM8 and p21/Cip1 in epithelial carcinoma cells in confluent conditions |
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