Liu, L.; Jung, S.; Lim, M.A.; Oh, C.; Piao, Y.; Ohm, S.; Shan, Y.; Kim, Y.I.; Won, H.; Chang, J.W.; Koo, B.S. Dual Blockage of P-cadherin and C-met Synergistically Inhibits the Growth of Head and Neck Cancer. Preprints2023, 2023101888. https://doi.org/10.20944/preprints202310.1888.v1
APA Style
Liu, L., Jung, S., Lim, M.A., Oh, C., Piao, Y., Ohm, S., Shan, Y., Kim, Y.I., Won, H., Chang, J.W., & Koo, B.S. (2023). Dual Blockage of P-cadherin and C-met Synergistically Inhibits the Growth of Head and Neck Cancer. Preprints. https://doi.org/10.20944/preprints202310.1888.v1
Chicago/Turabian Style
Liu, L., Jae Won Chang and Bon Seok Koo. 2023 "Dual Blockage of P-cadherin and C-met Synergistically Inhibits the Growth of Head and Neck Cancer" Preprints. https://doi.org/10.20944/preprints202310.1888.v1
Abstract
(1) Background: P-cadherin (CDH3) is a transmembrane protein that plays a crucial role in maintaining the structural integrity of epithelial tissue and homeostasis. Its role in carcinogenesis remains a subject of debate, as its behavior can vary depending on the molecular context and the specific tumor cell model under study. In this study, we explored the role of P-cadherin in head and neck squamous cell carcinoma (HNSCC) and the mechanism underlying its function. (2) Methods: We analyzed P-cadherin expression in HNSCC patients using The Cancer Genome Atlas (TCGA) database. For in vitro functional analysis, we conducted proliferation, migration, invasion, and western blot assays after either suppressing or overexpressing P-cadherin. For in vivo functional analysis, we utilized mouse xenograft models. (3) Results: P-cadherin was significantly overex-pressed in tumor samples compared to normal samples in the TCGA-HNSCC cohort. P-cadherin knockdown resulted in decreased proliferation, migration, and invasion compared to control cells, while P-cadherin overexpression increased cell proliferation and migration in HNSCC cells. We discovered that c-Met functioned as an upstream regulator of P-cadherin. Surprisingly, we found that P-cadherin knockdown increased the phosphorylation of c-Met and STAT3. Combining P-cadherin siRNA with the c-Met inhibitor SU11274 resulted in a more effective reduction in HNSCC cell growth, both in vitro and in vivo, compared to either treatment alone. (4) Conclusions: Our study uncovered a previously unknown aspect of P-cadherin-mediated c-Met regulation. The enhanced activation of c-Met/STAT3 following P-cadherin inhibition could be responsible for the survival of resistant tumor cells. Therefore, dual inhibition of P-cadherin and c-Met may be a potentially effective approach for treating HNSCC.
Keywords
P-cadherin; c-Met; cell proliferation; cell migration; Head and neck cancer
Subject
Biology and Life Sciences, Biochemistry and Molecular Biology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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