Pepsin promotes laryngopharyngeal neoplasia by modulating signaling pathways to induce cell proliferation
Pepsin plays an important role in laryngopharyngeal reflux (LPR), a risk factor for the development of hypopharyngeal squamous cell carcinomas (HPSCC). However, the role of pepsin in HPSCC is not clear. We show by immunohistochemistry that pepsin positivity occurs in a significant proportion of huma...
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| creator | Niu, Kai Guo, Chunjie Teng, Shiyong Zhou, Dandan Yu, Shuyuan Yin, Wanzhong Wang, Ping Zhu, Wei Duan, Maoli |
| description | Pepsin plays an important role in laryngopharyngeal reflux (LPR), a risk factor for the development of hypopharyngeal squamous cell carcinomas (HPSCC). However, the role of pepsin in HPSCC is not clear. We show by immunohistochemistry that pepsin positivity occurs in a significant proportion of human primary HPSCC specimens, and in many cases matched adjacent uninvolved epithelia are negative for pepsin. Pepsin positivity is associated with nodal involvement, suggesting that pepsin may have a role in metastasis. Treatment of FaDu cancer cells with pepsin increased cell proliferation, possibly by inducing G1/S transition. We also observed significant changes in expression of genes involved in NF-kappaB, TRAIL and Notch signaling. Our data suggest that pepsin plays an important role in HPSCC and that targeting pepsin could have potential therapeutic benefits. |
| doi_str_mv | 10.1371/journal.pone.0227408 |
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However, the role of pepsin in HPSCC is not clear. We show by immunohistochemistry that pepsin positivity occurs in a significant proportion of human primary HPSCC specimens, and in many cases matched adjacent uninvolved epithelia are negative for pepsin. Pepsin positivity is associated with nodal involvement, suggesting that pepsin may have a role in metastasis. Treatment of FaDu cancer cells with pepsin increased cell proliferation, possibly by inducing G1/S transition. We also observed significant changes in expression of genes involved in NF-kappaB, TRAIL and Notch signaling. Our data suggest that pepsin plays an important role in HPSCC and that targeting pepsin could have potential therapeutic benefits.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0227408</identifier><identifier>PMID: 31940393</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Aged ; Biology and Life Sciences ; Biotechnology ; Cancer ; Carcinoma, Squamous Cell - metabolism ; Carcinoma, Squamous Cell - pathology ; Cell cycle ; Cell growth ; Cell Line, Tumor ; Cell proliferation ; Cytokines ; Esophagus ; Female ; Flow cytometry ; G1 Phase ; Gene expression ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Laryngeal Neoplasms - metabolism ; Laryngeal Neoplasms - pathology ; Male ; Medicine and Health Sciences ; Metastases ; Microscopy ; Middle Aged ; Neoplasm Metastasis ; Neoplasm Proteins - metabolism ; NF-κB protein ; Otolaryngology ; Pepsin ; Pepsin A - metabolism ; Pepsin A - pharmacology ; Pharyngeal Neoplasms - metabolism ; Pharyngeal Neoplasms - pathology ; Research and Analysis Methods ; Risk analysis ; Risk factors ; S Phase ; Signal Transduction ; Signaling ; Squamous cell carcinoma ; Supervision ; Surgery ; Throat cancer</subject><ispartof>PloS one, 2020, Vol.15 (1), p.e0227408-e0227408</ispartof><rights>2020 Niu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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However, the role of pepsin in HPSCC is not clear. We show by immunohistochemistry that pepsin positivity occurs in a significant proportion of human primary HPSCC specimens, and in many cases matched adjacent uninvolved epithelia are negative for pepsin. Pepsin positivity is associated with nodal involvement, suggesting that pepsin may have a role in metastasis. Treatment of FaDu cancer cells with pepsin increased cell proliferation, possibly by inducing G1/S transition. We also observed significant changes in expression of genes involved in NF-kappaB, TRAIL and Notch signaling. Our data suggest that pepsin plays an important role in HPSCC and that targeting pepsin could have potential therapeutic benefits.</description><subject>Aged</subject><subject>Biology and Life Sciences</subject><subject>Biotechnology</subject><subject>Cancer</subject><subject>Carcinoma, Squamous Cell - metabolism</subject><subject>Carcinoma, Squamous Cell - pathology</subject><subject>Cell cycle</subject><subject>Cell growth</subject><subject>Cell Line, Tumor</subject><subject>Cell proliferation</subject><subject>Cytokines</subject><subject>Esophagus</subject><subject>Female</subject><subject>Flow cytometry</subject><subject>G1 Phase</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Laryngeal Neoplasms - metabolism</subject><subject>Laryngeal Neoplasms - pathology</subject><subject>Male</subject><subject>Medicine and Health Sciences</subject><subject>Metastases</subject><subject>Microscopy</subject><subject>Middle Aged</subject><subject>Neoplasm Metastasis</subject><subject>Neoplasm Proteins - 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| subjects | Aged Biology and Life Sciences Biotechnology Cancer Carcinoma, Squamous Cell - metabolism Carcinoma, Squamous Cell - pathology Cell cycle Cell growth Cell Line, Tumor Cell proliferation Cytokines Esophagus Female Flow cytometry G1 Phase Gene expression Gene Expression Regulation, Neoplastic Humans Immunohistochemistry Laryngeal Neoplasms - metabolism Laryngeal Neoplasms - pathology Male Medicine and Health Sciences Metastases Microscopy Middle Aged Neoplasm Metastasis Neoplasm Proteins - metabolism NF-κB protein Otolaryngology Pepsin Pepsin A - metabolism Pepsin A - pharmacology Pharyngeal Neoplasms - metabolism Pharyngeal Neoplasms - pathology Research and Analysis Methods Risk analysis Risk factors S Phase Signal Transduction Signaling Squamous cell carcinoma Supervision Surgery Throat cancer |
| title | Pepsin promotes laryngopharyngeal neoplasia by modulating signaling pathways to induce cell proliferation |
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