Related Experiment Video

Updated: Aug 26, 2025

Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence

Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence

Published on: January 7, 2019

Doublecortin-like kinase 1 is a therapeutic target in squamous cell carcinoma

David Standing¹, Levi Arnold¹, Prasad Dandawate¹

¹Department of Cancer Biology, University of Kansas Medical Center, Kansas City, Kansas, USA.

Molecular Carcinogenesis

|October 11, 2022

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.

Insights

Doublecortin like kinase 1 (DCLK1) is elevated in squamous cell carcinoma (SCC), driving tumor growth and poorer survival. A new inhibitor, DiFiD, selectively targets DCLK1, offering a promising therapeutic strategy for SCC.

Area of Science:

Oncology
Molecular Biology
Cancer Research

Background:

Doublecortin like kinase 1 (DCLK1) is implicated in various cancers.
The role of DCLK1 in squamous cell carcinoma (SCC) is not well understood.
DCLK1's function in head and neck SCC (HNSCC) and anal SCC (ASCC) requires investigation.

Purpose of the Study:

To investigate DCLK1 expression and its correlation with clinicopathological features in HNSCC and ASCC.
To elucidate the functional role of DCLK1 in SCC tumorigenesis.
To identify and evaluate a selective DCLK1 inhibitor for SCC treatment.

Main Methods:

DCLK1 expression was analyzed in patient SCC tissues.
DCLK1 was suppressed using short hairpin RNA (shRNA) in HNSCC cell lines.
The selective DCLK1 inhibitor DiFiD was tested in vitro and in vivo using HNSCC and ASCC models.

Main Results:

DCLK1 expression was elevated in SCC tissues, correlating with advanced cancer and reduced survival.
DCLK1 suppression reduced tumor growth, spheroid formation, and migration in HNSCC cells.
DiFiD selectively inhibited DCLK1, inducing G2/M arrest and apoptosis, and suppressed tumor growth in HNSCC and ASCC xenografts.

Conclusions:

DCLK1 is a critical driver of SCC growth and progression.
Targeting DCLK1 with selective inhibitors like DiFiD shows therapeutic potential for SCC.
DCLK1 inhibition represents a promising strategy for treating aggressive SCC subtypes, including HPV-negative HNSCC.

Read full analysis

Keywords:

DCLK1 DiFiD HNSCC anal SCC patient derived xenograft therapy

More Related Videos

Identification of Novel CK2 Kinase Substrates Using a Versatile Biochemical Approach

Identification of Novel CK2 Kinase Substrates Using a Versatile Biochemical Approach

Published on: February 21, 2019

Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies

Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies

Published on: September 30, 2016

Related Concept Videos

Inhibition of Cdk Activity

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...

M-Cdk Drives Transition Into Mitosis

M-Cdk Drives Transition Into Mitosis

Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...

Targeted Cancer Therapies

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...

Abnormal Proliferation

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...

mTOR Signaling and Cancer Progression

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...

Mitogens and the Cell Cycle

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...

Articles linked to this work by shared authors, journal, and citation graph.

Characterization of the New Pentafluorosulfanyl-Substituted Chalcone 246TMP-3SF5 as a Potential New Treatment Option Against Hepatocellular Carcinoma.

Cancers·2026

In Vitro and In Silico Evaluation of the Anti-Infective Potential of EF24-Analogous Curcuminoids: Antiprotozoal Activity and HIV-1 Ribonuclease H Inhibition.

Pathogens (Basel, Switzerland)·2026

Pediatric Extrapolation in Neuropsychiatric Drug Development: Leveraging Pharmacokinetic and Pharmacodynamic Strategies to Facilitate FDA Approvals.

Clinical pharmacology and therapeutics·2026

Targeting notch signaling pathway in esophageal cancer: from molecular insights to therapies.

Oncology reviews·2026

Rapid On-Site Next-Generation Sequencing: An Alternative to Single-Gene and Send-Out Testing in Non-Small Cell Lung Cancer and Colorectal Cancer in a Community Pathology Laboratory Setting.

The Journal of molecular diagnostics : JMD·2026

Novel N-chloroacetyl-2-pyrazoline analogs with 2-naphthyl and ferrocenyl groups: targeting histamine receptor H1 to overcome colorectal cancer drug resistance.

Cancer drug resistance (Alhambra, Calif.)·2026

See all related articles