Doublecortin-like kinase 1 is a therapeutic target in squamous cell carcinoma
Correction(s) for this article
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Corrigendum
- Volume 62Issue 8Molecular Carcinogenesis
- pages: 1240-1241
- First Published online: June 21, 2023
David Standing
Department of Cancer Biology, University of Kansas Medical Center, Kansas City, Kansas, USA
Search for more papers by this authorLevi Arnold
Department of Cancer Biology, University of Kansas Medical Center, Kansas City, Kansas, USA
Search for more papers by this authorPrasad Dandawate
Department of Cancer Biology, University of Kansas Medical Center, Kansas City, Kansas, USA
Search for more papers by this authorBrendan Ottemann
Department of Otolaryngology, University of Kansas Medical Center, Kansas City, Kansas, USA
Search for more papers by this authorVusala Snyder
Department of Otolaryngology, University of Kansas Medical Center, Kansas City, Kansas, USA
Search for more papers by this authorSivapriya Ponnurangam
Department of Cancer Biology, University of Kansas Medical Center, Kansas City, Kansas, USA
Search for more papers by this authorAfreen Sayed
Department of Cancer Biology, University of Kansas Medical Center, Kansas City, Kansas, USA
Search for more papers by this authorDharmalingam Subramaniam
Department of Cancer Biology, University of Kansas Medical Center, Kansas City, Kansas, USA
Search for more papers by this authorPugazhendhi Srinivasan
Department of Cancer Biology, University of Kansas Medical Center, Kansas City, Kansas, USA
Search for more papers by this authorSonali Choudhury
Department of Cancer Biology, University of Kansas Medical Center, Kansas City, Kansas, USA
Search for more papers by this authorJacob New
Department of Otolaryngology, University of Kansas Medical Center, Kansas City, Kansas, USA
Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, Kansas, USA
Search for more papers by this authorDeep Kwatra
Department of Cancer Biology, University of Kansas Medical Center, Kansas City, Kansas, USA
Search for more papers by this authorPrabhu Ramamoorthy
Department of Cancer Biology, University of Kansas Medical Center, Kansas City, Kansas, USA
Search for more papers by this authorBadal C. Roy
Department of General Surgery, University of Kansas Medical Center, Kansas City, Kansas, USA
Search for more papers by this authorMelissa Shadoin
Department of Otolaryngology, University of Kansas Medical Center, Kansas City, Kansas, USA
Search for more papers by this authorRaed Al-Rajabi
Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas, USA
Search for more papers by this authorMaura O'Neil
Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, Kansas, USA
Search for more papers by this authorSumedha Gunewardena
Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, Kansas, USA
Search for more papers by this authorJohn Ashcraft
Department of General Surgery, University of Kansas Medical Center, Kansas City, Kansas, USA
Search for more papers by this authorShahid Umar
Department of General Surgery, University of Kansas Medical Center, Kansas City, Kansas, USA
Search for more papers by this authorScott J. Weir
Department of Cancer Biology, University of Kansas Medical Center, Kansas City, Kansas, USA
Institute for Advancing Medical Innovation, University of Kansas Medical Center, Kansas City, Kansas, USA
Search for more papers by this authorOssama Tawfik
Department of Pathology, Saint Luke's Health System, Kansas City, Missouri, USA
MAWD Pathology Group, Kansas City, Kansas, USA
Search for more papers by this authorSubhash B. Padhye
Department of Chemistry, Interdisciplinary Science and Technology Research Academy, University of Pune, Pune, India
Search for more papers by this authorBernhard Biersack
Department of Chemistry, University of Bayreuth, Bayreuth, Germany
Search for more papers by this authorCorresponding Author
Shrikant Anant
Department of Cancer Biology, University of Kansas Medical Center, Kansas City, Kansas, USA
Correspondence Sufi Mary Thomas, PhD, Departments of Otolaryngology, Cancer Biology and Anatomy and Cell Biology, University of Kansas Medical Center, 3901 Rainbow Blvd., MS 3040, Wahl Hall East 4031, Kansas City, KS 66160, USA.
Email: [email protected]
Shrikant Anant, PhD, Department of Cancer Biology, University of Kansas Cancer Center, and University of Kansas Medical Center, 3901 Rainbow Blvd., Wahl Hall East 4019, Kansas City, KS 66160, USA.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Sufi Mary Thomas
Department of Cancer Biology, University of Kansas Medical Center, Kansas City, Kansas, USA
Department of Otolaryngology, University of Kansas Medical Center, Kansas City, Kansas, USA
Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, Kansas, USA
Correspondence Sufi Mary Thomas, PhD, Departments of Otolaryngology, Cancer Biology and Anatomy and Cell Biology, University of Kansas Medical Center, 3901 Rainbow Blvd., MS 3040, Wahl Hall East 4031, Kansas City, KS 66160, USA.
Email: [email protected]
Shrikant Anant, PhD, Department of Cancer Biology, University of Kansas Cancer Center, and University of Kansas Medical Center, 3901 Rainbow Blvd., Wahl Hall East 4019, Kansas City, KS 66160, USA.
Email: [email protected]
Search for more papers by this authorDavid Standing
Department of Cancer Biology, University of Kansas Medical Center, Kansas City, Kansas, USA
Search for more papers by this authorLevi Arnold
Department of Cancer Biology, University of Kansas Medical Center, Kansas City, Kansas, USA
Search for more papers by this authorPrasad Dandawate
Department of Cancer Biology, University of Kansas Medical Center, Kansas City, Kansas, USA
Search for more papers by this authorBrendan Ottemann
Department of Otolaryngology, University of Kansas Medical Center, Kansas City, Kansas, USA
Search for more papers by this authorVusala Snyder
Department of Otolaryngology, University of Kansas Medical Center, Kansas City, Kansas, USA
Search for more papers by this authorSivapriya Ponnurangam
Department of Cancer Biology, University of Kansas Medical Center, Kansas City, Kansas, USA
Search for more papers by this authorAfreen Sayed
Department of Cancer Biology, University of Kansas Medical Center, Kansas City, Kansas, USA
Search for more papers by this authorDharmalingam Subramaniam
Department of Cancer Biology, University of Kansas Medical Center, Kansas City, Kansas, USA
Search for more papers by this authorPugazhendhi Srinivasan
Department of Cancer Biology, University of Kansas Medical Center, Kansas City, Kansas, USA
Search for more papers by this authorSonali Choudhury
Department of Cancer Biology, University of Kansas Medical Center, Kansas City, Kansas, USA
Search for more papers by this authorJacob New
Department of Otolaryngology, University of Kansas Medical Center, Kansas City, Kansas, USA
Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, Kansas, USA
Search for more papers by this authorDeep Kwatra
Department of Cancer Biology, University of Kansas Medical Center, Kansas City, Kansas, USA
Search for more papers by this authorPrabhu Ramamoorthy
Department of Cancer Biology, University of Kansas Medical Center, Kansas City, Kansas, USA
Search for more papers by this authorBadal C. Roy
Department of General Surgery, University of Kansas Medical Center, Kansas City, Kansas, USA
Search for more papers by this authorMelissa Shadoin
Department of Otolaryngology, University of Kansas Medical Center, Kansas City, Kansas, USA
Search for more papers by this authorRaed Al-Rajabi
Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas, USA
Search for more papers by this authorMaura O'Neil
Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, Kansas, USA
Search for more papers by this authorSumedha Gunewardena
Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, Kansas, USA
Search for more papers by this authorJohn Ashcraft
Department of General Surgery, University of Kansas Medical Center, Kansas City, Kansas, USA
Search for more papers by this authorShahid Umar
Department of General Surgery, University of Kansas Medical Center, Kansas City, Kansas, USA
Search for more papers by this authorScott J. Weir
Department of Cancer Biology, University of Kansas Medical Center, Kansas City, Kansas, USA
Institute for Advancing Medical Innovation, University of Kansas Medical Center, Kansas City, Kansas, USA
Search for more papers by this authorOssama Tawfik
Department of Pathology, Saint Luke's Health System, Kansas City, Missouri, USA
MAWD Pathology Group, Kansas City, Kansas, USA
Search for more papers by this authorSubhash B. Padhye
Department of Chemistry, Interdisciplinary Science and Technology Research Academy, University of Pune, Pune, India
Search for more papers by this authorBernhard Biersack
Department of Chemistry, University of Bayreuth, Bayreuth, Germany
Search for more papers by this authorCorresponding Author
Shrikant Anant
Department of Cancer Biology, University of Kansas Medical Center, Kansas City, Kansas, USA
Correspondence Sufi Mary Thomas, PhD, Departments of Otolaryngology, Cancer Biology and Anatomy and Cell Biology, University of Kansas Medical Center, 3901 Rainbow Blvd., MS 3040, Wahl Hall East 4031, Kansas City, KS 66160, USA.
Email: [email protected]
Shrikant Anant, PhD, Department of Cancer Biology, University of Kansas Cancer Center, and University of Kansas Medical Center, 3901 Rainbow Blvd., Wahl Hall East 4019, Kansas City, KS 66160, USA.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Sufi Mary Thomas
Department of Cancer Biology, University of Kansas Medical Center, Kansas City, Kansas, USA
Department of Otolaryngology, University of Kansas Medical Center, Kansas City, Kansas, USA
Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, Kansas, USA
Correspondence Sufi Mary Thomas, PhD, Departments of Otolaryngology, Cancer Biology and Anatomy and Cell Biology, University of Kansas Medical Center, 3901 Rainbow Blvd., MS 3040, Wahl Hall East 4031, Kansas City, KS 66160, USA.
Email: [email protected]
Shrikant Anant, PhD, Department of Cancer Biology, University of Kansas Cancer Center, and University of Kansas Medical Center, 3901 Rainbow Blvd., Wahl Hall East 4019, Kansas City, KS 66160, USA.
Email: [email protected]
Search for more papers by this authorDavid Standing and Levi Arnold contributed equally to this study.
Abstract
Doublecortin like kinase 1 (DCLK1) plays a crucial role in several cancers including colon and pancreatic adenocarcinomas. However, its role in squamous cell carcinoma (SCC) remains unknown. To this end, we examined DCLK1 expression in head and neck SCC (HNSCC) and anal SCC (ASCC). We found that DCLK1 is elevated in patient SCC tissue, which correlated with cancer progression and poorer overall survival. Furthermore, DCLK1 expression is significantly elevated in human papilloma virus negative HNSCC, which are typically aggressive with poor responses to therapy. To understand the role of DCLK1 in tumorigenesis, we used specific shRNA to suppress DCLK1 expression. This significantly reduced tumor growth, spheroid formation, and migration of HNSCC cancer cells. To further the translational relevance of our studies, we sought to identify a selective DCLK1 inhibitor. Current attempts to target DCLK1 using pharmacologic approaches have relied on nonspecific suppression of DCLK1 kinase activity. Here, we demonstrate that DiFiD (3,5-bis [2,4-difluorobenzylidene]−4-piperidone) binds to DCLK1 with high selectivity. Moreover, DiFiD mediated suppression of DCLK1 led to G2/M arrest and apoptosis and significantly suppressed tumor growth of HNSCC xenografts and ASCC patient derived xenografts, supporting that DCLK1 is critical for SCC growth.
Open Research
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Supporting Information
| Filename | Description |
|---|---|
| mc23472-sup-0001-Supplementary_Figure_1.TIF467.9 KB | Supplementary Figure 1. |
| mc23472-sup-0002-Supplementary_Figure_2.TIF163.7 KB | Supplementary Figure 2. |
| mc23472-sup-0003-Supplementary_Figure_3.TIF164.1 KB | Supplementary Figure 3. |
| mc23472-sup-0004-Supplementary_Figure_4.TIF236 KB | Supplementary Figure 4. |
| mc23472-sup-0005-Supplementary_Figure_5.TIF68.2 KB | Supplementary Figure 5 |
| mc23472-sup-0006-Supplementary_Figure_6.TIF157.6 KB | Supplemental Figure 6. |
| mc23472-sup-0007-DCLK1_Manuscript_Supplemental_Methods_8_30_22.docx38.3 KB | Supporting information. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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