Metformin Induces Different Responses in Clear Cell Renal Cell Carcinoma Caki Cell Lines
<div><p>Clear cell renal cell carcinoma (ccRCC) is the most common and lethal form of urological cancer diagnosed globally. Mutations of the von Hippel-Lindau (VHL) tumor-suppressor gene and the resultant overexpression of hypoxia-inducible factor (HIF)-1α protein are considered hallmark...
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| مؤلفون آخرون: | , , , |
| منشور في: |
2019
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| _version_ | 1864513521779212288 |
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| author | Mazhar Pasha (11197767) |
| author2 | Siveen K. Sivaraman (17280685) Ronald Frantz (18134095) Abdelali Agouni (181926) Shankar Munusamy (14590810) |
| author2_role | author author author author |
| author_facet | Mazhar Pasha (11197767) Siveen K. Sivaraman (17280685) Ronald Frantz (18134095) Abdelali Agouni (181926) Shankar Munusamy (14590810) |
| author_role | author |
| dc.creator.none.fl_str_mv | Mazhar Pasha (11197767) Siveen K. Sivaraman (17280685) Ronald Frantz (18134095) Abdelali Agouni (181926) Shankar Munusamy (14590810) |
| dc.date.none.fl_str_mv | 2019-03-22T03:00:00Z |
| dc.identifier.none.fl_str_mv | 10.3390/biom9030113 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Metformin_Induces_Different_Responses_in_Clear_Cell_Renal_Cell_Carcinoma_Caki_Cell_Lines/25378837 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biological sciences Biochemistry and cell biology renal cell carcinoma von Hippel-Lindau hypoxia-inducible factor AMP-activated kinase metformin |
| dc.title.none.fl_str_mv | Metformin Induces Different Responses in Clear Cell Renal Cell Carcinoma Caki Cell Lines |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <div><p>Clear cell renal cell carcinoma (ccRCC) is the most common and lethal form of urological cancer diagnosed globally. Mutations of the von Hippel-Lindau (VHL) tumor-suppressor gene and the resultant overexpression of hypoxia-inducible factor (HIF)-1α protein are considered hallmarks of ccRCC. Persistently activated HIF-1α is associated with increased cell proliferation, angiogenesis, and epithelial–mesenchymal transition (EMT), consequently leading to ccRCC progression and metastasis to other organs. However, the VHL status alone cannot predict the differential sensitivity of ccRCC to cancer treatments, which suggests that other molecular differences may contribute to the differential response of ccRCC cells to drug therapies. In this study, we investigated the response to metformin (an antidiabetic drug) of two human ccRCC cell lines Caki-1 and Caki-2, which express wild-type VHL. Our findings demonstrate a differential response between the two ccRCC cell lines studied, with Caki-2 cells being more sensitive to metformin compared to Caki-1 cells, which could be linked to the differential expression of HIF-1 despite both cell lines carrying a wild-type VHL. Our study unveils the therapeutic potential of metformin to inhibit the progression of ccRCC in vitro. Additional preclinical and clinical studies are required to ascertain the therapeutic efficacy of metformin against ccRCC.</p><p> </p></div><h2>Other Information</h2> <p> Published in: Biomolecules<br> License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3390/biom9030113" target="_blank">https://dx.doi.org/10.3390/biom9030113</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_fbf2dc3c976d4a8147d91024660d06f7 |
| identifier_str_mv | 10.3390/biom9030113 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/25378837 |
| publishDate | 2019 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Metformin Induces Different Responses in Clear Cell Renal Cell Carcinoma Caki Cell LinesMazhar Pasha (11197767)Siveen K. Sivaraman (17280685)Ronald Frantz (18134095)Abdelali Agouni (181926)Shankar Munusamy (14590810)Biological sciencesBiochemistry and cell biologyrenal cell carcinomavon Hippel-Lindauhypoxia-inducible factorAMP-activated kinasemetformin<div><p>Clear cell renal cell carcinoma (ccRCC) is the most common and lethal form of urological cancer diagnosed globally. Mutations of the von Hippel-Lindau (VHL) tumor-suppressor gene and the resultant overexpression of hypoxia-inducible factor (HIF)-1α protein are considered hallmarks of ccRCC. Persistently activated HIF-1α is associated with increased cell proliferation, angiogenesis, and epithelial–mesenchymal transition (EMT), consequently leading to ccRCC progression and metastasis to other organs. However, the VHL status alone cannot predict the differential sensitivity of ccRCC to cancer treatments, which suggests that other molecular differences may contribute to the differential response of ccRCC cells to drug therapies. In this study, we investigated the response to metformin (an antidiabetic drug) of two human ccRCC cell lines Caki-1 and Caki-2, which express wild-type VHL. Our findings demonstrate a differential response between the two ccRCC cell lines studied, with Caki-2 cells being more sensitive to metformin compared to Caki-1 cells, which could be linked to the differential expression of HIF-1 despite both cell lines carrying a wild-type VHL. Our study unveils the therapeutic potential of metformin to inhibit the progression of ccRCC in vitro. Additional preclinical and clinical studies are required to ascertain the therapeutic efficacy of metformin against ccRCC.</p><p> </p></div><h2>Other Information</h2> <p> Published in: Biomolecules<br> License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3390/biom9030113" target="_blank">https://dx.doi.org/10.3390/biom9030113</a></p>2019-03-22T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.3390/biom9030113https://figshare.com/articles/journal_contribution/Metformin_Induces_Different_Responses_in_Clear_Cell_Renal_Cell_Carcinoma_Caki_Cell_Lines/25378837CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/253788372019-03-22T03:00:00Z |
| spellingShingle | Metformin Induces Different Responses in Clear Cell Renal Cell Carcinoma Caki Cell Lines Mazhar Pasha (11197767) Biological sciences Biochemistry and cell biology renal cell carcinoma von Hippel-Lindau hypoxia-inducible factor AMP-activated kinase metformin |
| status_str | publishedVersion |
| title | Metformin Induces Different Responses in Clear Cell Renal Cell Carcinoma Caki Cell Lines |
| title_full | Metformin Induces Different Responses in Clear Cell Renal Cell Carcinoma Caki Cell Lines |
| title_fullStr | Metformin Induces Different Responses in Clear Cell Renal Cell Carcinoma Caki Cell Lines |
| title_full_unstemmed | Metformin Induces Different Responses in Clear Cell Renal Cell Carcinoma Caki Cell Lines |
| title_short | Metformin Induces Different Responses in Clear Cell Renal Cell Carcinoma Caki Cell Lines |
| title_sort | Metformin Induces Different Responses in Clear Cell Renal Cell Carcinoma Caki Cell Lines |
| topic | Biological sciences Biochemistry and cell biology renal cell carcinoma von Hippel-Lindau hypoxia-inducible factor AMP-activated kinase metformin |