DCLK1 Regulates Tumor Stemness and Cisplatin Resistance in Non-small Cell Lung Cancer via ABCD-Member-4
Chemoresistance cells have features similar to cancer stem cells. Elimination of these cells is an effective therapeutic strategy to clinically combat chemoresistance non-small cell lung cancer (NSCLC). Here, we demonstrate that Doublecortin-like kinase1 (DCLK1) is the key to developing chemoresista...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-09-01
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| Series: | Molecular Therapy: Oncolytics |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2372770520300759 |
| _version_ | 1819038838682550272 |
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| author | Janani Panneerselvam Priyanga Mohandoss Ravi Patel Hamza Gillan Michael Li Kirtana Kumar DangHuy Nguyen Nathaniel Weygant Dongfeng Qu Kamille Pitts Stanley Lightfoot Chinthalapally Rao Courtney Houchen Michael Bronze Parthasarathy Chandrakesan |
| author_facet | Janani Panneerselvam Priyanga Mohandoss Ravi Patel Hamza Gillan Michael Li Kirtana Kumar DangHuy Nguyen Nathaniel Weygant Dongfeng Qu Kamille Pitts Stanley Lightfoot Chinthalapally Rao Courtney Houchen Michael Bronze Parthasarathy Chandrakesan |
| author_sort | Janani Panneerselvam |
| collection | DOAJ |
| description | Chemoresistance cells have features similar to cancer stem cells. Elimination of these cells is an effective therapeutic strategy to clinically combat chemoresistance non-small cell lung cancer (NSCLC). Here, we demonstrate that Doublecortin-like kinase1 (DCLK1) is the key to developing chemoresistance and associated stemness in NSCLC. DCLK1 is highly expressed in human lung adenocarcinoma and strongly correlated with stemness. Silencing DCLK1 inhibits NSCLC cell primary and secondary spheroid formation, which is the prerequisite feature of tumor stem cells. DCLK1 inhibition reduced NSCLC cell migration/invasion in vitro and induced tumor growth inhibition in vivo. NSCLC cells responded differently to cisplatin treatment; indeed, the clonogenic ability of all NSCLC cells was reduced. We found that the cisplatin-resistant NSCLC cells gain the expression of DCLK1 compared with their parental control. However, DCLK1 inhibition in cisplatin-resistance NSCLC cells reverses the tumor cell resistance to cisplatin and reduced tumor self-renewal ability. Specifically, we found that DCLK1-mediated cisplatin resistance in NSCLC is via an ABC subfamily member 4 (ABCD4)-dependent mechanism. Our data demonstrate that increased expression of DCLK1 is associated with chemoresistance and enhanced cancer stem cell-like features in NSCLC. Targeting DCLK1 using gene knockdown/knockout strategies alone or in combination with cisplatin may represent a novel therapeutic strategy to treat NSCLC. |
| first_indexed | 2024-12-21T08:43:40Z |
| format | Article |
| id | doaj.art-06ca05c4186b44ef85df781d0e227141 |
| institution | Directory Open Access Journal |
| issn | 2372-7705 |
| language | English |
| last_indexed | 2024-12-21T08:43:40Z |
| publishDate | 2020-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Oncolytics |
| spelling | doaj.art-06ca05c4186b44ef85df781d0e2271412022-12-21T19:09:52ZengElsevierMolecular Therapy: Oncolytics2372-77052020-09-01182436DCLK1 Regulates Tumor Stemness and Cisplatin Resistance in Non-small Cell Lung Cancer via ABCD-Member-4Janani Panneerselvam0Priyanga Mohandoss1Ravi Patel2Hamza Gillan3Michael Li4Kirtana Kumar5DangHuy Nguyen6Nathaniel Weygant7Dongfeng Qu8Kamille Pitts9Stanley Lightfoot10Chinthalapally Rao11Courtney Houchen12Michael Bronze13Parthasarathy Chandrakesan14Department of Medicine, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USADepartment of Biomedical Engineering, SRM University, Chennai, IndiaDepartment of Medicine, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USADepartment of Medicine, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USADepartment of Medicine, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USADepartment of Medicine, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USADepartment of Medicine, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USADepartment of Medicine, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USADepartment of Medicine, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USADepartment of Medicine, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USADepartment of Medicine, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USADepartment of Medicine, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA; Department of Veterans Affairs Medical Center, Oklahoma City, OK 73104, USADepartment of Medicine, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA; Department of Veterans Affairs Medical Center, Oklahoma City, OK 73104, USADepartment of Medicine, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USADepartment of Medicine, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA; Corresponding author: Parthasarathy Chandrakesan, MPhil, PhD, Department of Medicine, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.Chemoresistance cells have features similar to cancer stem cells. Elimination of these cells is an effective therapeutic strategy to clinically combat chemoresistance non-small cell lung cancer (NSCLC). Here, we demonstrate that Doublecortin-like kinase1 (DCLK1) is the key to developing chemoresistance and associated stemness in NSCLC. DCLK1 is highly expressed in human lung adenocarcinoma and strongly correlated with stemness. Silencing DCLK1 inhibits NSCLC cell primary and secondary spheroid formation, which is the prerequisite feature of tumor stem cells. DCLK1 inhibition reduced NSCLC cell migration/invasion in vitro and induced tumor growth inhibition in vivo. NSCLC cells responded differently to cisplatin treatment; indeed, the clonogenic ability of all NSCLC cells was reduced. We found that the cisplatin-resistant NSCLC cells gain the expression of DCLK1 compared with their parental control. However, DCLK1 inhibition in cisplatin-resistance NSCLC cells reverses the tumor cell resistance to cisplatin and reduced tumor self-renewal ability. Specifically, we found that DCLK1-mediated cisplatin resistance in NSCLC is via an ABC subfamily member 4 (ABCD4)-dependent mechanism. Our data demonstrate that increased expression of DCLK1 is associated with chemoresistance and enhanced cancer stem cell-like features in NSCLC. Targeting DCLK1 using gene knockdown/knockout strategies alone or in combination with cisplatin may represent a novel therapeutic strategy to treat NSCLC.http://www.sciencedirect.com/science/article/pii/S2372770520300759cisplatin resistancenon-small cell lung cancerChemoresistanceDCLK1ABC transportersABCD4 |
| spellingShingle | Janani Panneerselvam Priyanga Mohandoss Ravi Patel Hamza Gillan Michael Li Kirtana Kumar DangHuy Nguyen Nathaniel Weygant Dongfeng Qu Kamille Pitts Stanley Lightfoot Chinthalapally Rao Courtney Houchen Michael Bronze Parthasarathy Chandrakesan DCLK1 Regulates Tumor Stemness and Cisplatin Resistance in Non-small Cell Lung Cancer via ABCD-Member-4 Molecular Therapy: Oncolytics cisplatin resistance non-small cell lung cancer Chemoresistance DCLK1 ABC transporters ABCD4 |
| title | DCLK1 Regulates Tumor Stemness and Cisplatin Resistance in Non-small Cell Lung Cancer via ABCD-Member-4 |
| title_full | DCLK1 Regulates Tumor Stemness and Cisplatin Resistance in Non-small Cell Lung Cancer via ABCD-Member-4 |
| title_fullStr | DCLK1 Regulates Tumor Stemness and Cisplatin Resistance in Non-small Cell Lung Cancer via ABCD-Member-4 |
| title_full_unstemmed | DCLK1 Regulates Tumor Stemness and Cisplatin Resistance in Non-small Cell Lung Cancer via ABCD-Member-4 |
| title_short | DCLK1 Regulates Tumor Stemness and Cisplatin Resistance in Non-small Cell Lung Cancer via ABCD-Member-4 |
| title_sort | dclk1 regulates tumor stemness and cisplatin resistance in non small cell lung cancer via abcd member 4 |
| topic | cisplatin resistance non-small cell lung cancer Chemoresistance DCLK1 ABC transporters ABCD4 |
| url | http://www.sciencedirect.com/science/article/pii/S2372770520300759 |
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