Inhibition of mesothelin as a novel strategy for targeting cancer cells.
Mesothelin, a differentiation antigen present in a series of malignancies such as mesothelioma, ovarian, lung and pancreatic cancer, has been studied as a marker for diagnosis and a target for immunotherapy. We, however, were interested in evaluating the effects of direct targeting of Mesothelin on...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3317639?pdf=render |
| _version_ | 1811274252432703488 |
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| author | Kun Wang Vidya Bodempudi Zhengian Liu Emma Borrego-Diaz Farnaz Yamoutpoor Anna Meyer Richard A Woo Weihong Pan Arkadiusz Z Dudek Mojtaba S Olyaee Tuba Esfandyari Faris Farassati |
| author_facet | Kun Wang Vidya Bodempudi Zhengian Liu Emma Borrego-Diaz Farnaz Yamoutpoor Anna Meyer Richard A Woo Weihong Pan Arkadiusz Z Dudek Mojtaba S Olyaee Tuba Esfandyari Faris Farassati |
| author_sort | Kun Wang |
| collection | DOAJ |
| description | Mesothelin, a differentiation antigen present in a series of malignancies such as mesothelioma, ovarian, lung and pancreatic cancer, has been studied as a marker for diagnosis and a target for immunotherapy. We, however, were interested in evaluating the effects of direct targeting of Mesothelin on the viability of cancer cells as the first step towards developing a novel therapeutic strategy. We report here that gene specific silencing for Mesothelin by distinct methods (siRNA and microRNA) decreased viability of cancer cells from different origins such as mesothelioma (H2373), ovarian cancer (Skov3 and Ovcar-5) and pancreatic cancer (Miapaca2 and Panc-1). Additionally, the invasiveness of cancer cells was also significantly decreased upon such treatment. We then investigated pro-oncogenic signaling characteristics of cells upon mesothelin-silencing which revealed a significant decrease in phospho-ERK1 and PI3K/AKT activity. The molecular mechanism of reduced invasiveness was connected to the reduced expression of β-Catenin, an important marker of EMT (epithelial-mesenchymal transition). Ero1, a protein involved in clearing unfolded proteins and a member of the ER-Stress (endoplasmic reticulum-stress) pathway was also markedly reduced. Furthermore, Mesothelin silencing caused a significant increase in fraction of cancer cells in S-phase. In next step, treatment of ovarian cancer cells (OVca429) with a lentivirus expressing anti-mesothelin microRNA resulted in significant loss of viability, invasiveness, and morphological alterations. Therefore, we propose the inhibition of Mesothelin as a potential novel strategy for targeting human malignancies. |
| first_indexed | 2024-04-12T23:15:38Z |
| format | Article |
| id | doaj.art-00ea7089c1a64575811513a0a57777f5 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T23:15:38Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-00ea7089c1a64575811513a0a57777f52022-12-22T03:12:40ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0174e3321410.1371/journal.pone.0033214Inhibition of mesothelin as a novel strategy for targeting cancer cells.Kun WangVidya BodempudiZhengian LiuEmma Borrego-DiazFarnaz YamoutpoorAnna MeyerRichard A WooWeihong PanArkadiusz Z DudekMojtaba S OlyaeeTuba EsfandyariFaris FarassatiMesothelin, a differentiation antigen present in a series of malignancies such as mesothelioma, ovarian, lung and pancreatic cancer, has been studied as a marker for diagnosis and a target for immunotherapy. We, however, were interested in evaluating the effects of direct targeting of Mesothelin on the viability of cancer cells as the first step towards developing a novel therapeutic strategy. We report here that gene specific silencing for Mesothelin by distinct methods (siRNA and microRNA) decreased viability of cancer cells from different origins such as mesothelioma (H2373), ovarian cancer (Skov3 and Ovcar-5) and pancreatic cancer (Miapaca2 and Panc-1). Additionally, the invasiveness of cancer cells was also significantly decreased upon such treatment. We then investigated pro-oncogenic signaling characteristics of cells upon mesothelin-silencing which revealed a significant decrease in phospho-ERK1 and PI3K/AKT activity. The molecular mechanism of reduced invasiveness was connected to the reduced expression of β-Catenin, an important marker of EMT (epithelial-mesenchymal transition). Ero1, a protein involved in clearing unfolded proteins and a member of the ER-Stress (endoplasmic reticulum-stress) pathway was also markedly reduced. Furthermore, Mesothelin silencing caused a significant increase in fraction of cancer cells in S-phase. In next step, treatment of ovarian cancer cells (OVca429) with a lentivirus expressing anti-mesothelin microRNA resulted in significant loss of viability, invasiveness, and morphological alterations. Therefore, we propose the inhibition of Mesothelin as a potential novel strategy for targeting human malignancies.http://europepmc.org/articles/PMC3317639?pdf=render |
| spellingShingle | Kun Wang Vidya Bodempudi Zhengian Liu Emma Borrego-Diaz Farnaz Yamoutpoor Anna Meyer Richard A Woo Weihong Pan Arkadiusz Z Dudek Mojtaba S Olyaee Tuba Esfandyari Faris Farassati Inhibition of mesothelin as a novel strategy for targeting cancer cells. PLoS ONE |
| title | Inhibition of mesothelin as a novel strategy for targeting cancer cells. |
| title_full | Inhibition of mesothelin as a novel strategy for targeting cancer cells. |
| title_fullStr | Inhibition of mesothelin as a novel strategy for targeting cancer cells. |
| title_full_unstemmed | Inhibition of mesothelin as a novel strategy for targeting cancer cells. |
| title_short | Inhibition of mesothelin as a novel strategy for targeting cancer cells. |
| title_sort | inhibition of mesothelin as a novel strategy for targeting cancer cells |
| url | http://europepmc.org/articles/PMC3317639?pdf=render |
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