Related Experiment Video

Updated: May 2, 2026

Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies
09:29

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

Published on: September 30, 2016

13.4K

Protein kinase d as a potential chemotherapeutic target for colorectal cancer

Ning Wei1, Edward Chu, Peter Wipf

  • 1Authors' Affiliations: Division of Hematology-Oncology, Department of Medicine, University of Pittsburgh School of Medicine; Cancer Therapeutics Program, University of Pittsburgh Cancer Institute; and Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania.

Molecular Cancer Therapeutics
|March 18, 2014
PubMed

Insights

Protein kinase D (PKD) is crucial for colorectal cancer growth. Inhibiting PKD, particularly the PKD2 isoform, showed significant antitumor effects in cell lines and mouse models, suggesting PKD as a novel therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Protein kinase D (PKD) signaling is vital for cell functions including proliferation and survival.
  • The role of PKD in human colorectal cancer (CRC) development and progression remains largely unexplored.

Purpose of the Study:

  • To investigate PKD isoform expression in colorectal cancer.
  • To evaluate the efficacy of PKD inhibitors as an antitumor strategy for colorectal cancer.

Main Methods:

  • Assessed PKD isoform expression in human colon cancer cells.
  • Utilized small molecule PKD inhibitors (CRT0066101, kb-NB142-70) and PKD2-targeted siRNAs.
  • Conducted in vitro proliferation assays, cell cycle analysis, apoptosis studies, and Western blotting.
  • Evaluated tumor growth inhibition in HCT116 xenograft mouse models.

Main Results:

  • PKD2 was the predominant isoform in colon cancer cells; PKD1 was undetectable.
  • PKD inhibitors demonstrated low micromolar antiproliferative activity against CRC cell lines.
  • CRT0066101 induced G2-M phase arrest, apoptosis, inhibited AKT/ERK signaling, and suppressed NF-κB.
  • PKD2 suppression via siRNA mimicked inhibitor effects.
  • CRT0066101 significantly inhibited tumor growth in vivo.

Conclusions:

  • PKD signaling is a significant mediator of growth in colorectal cancer.
  • Targeting PKD, especially the PKD2 isoform, represents a promising novel therapeutic strategy for colorectal cancer treatment.

More Related Videos

Using Human Differentially Expressed Gene Lists to Perform Downstream Pathway Enrichment Analysis and Target Prioritization03:08

Using Human Differentially Expressed Gene Lists to Perform Downstream Pathway Enrichment Analysis and Target Prioritization

Published on: October 3, 2025

1.1K
Identification of Novel CK2 Kinase Substrates Using a Versatile Biochemical Approach11:11

Identification of Novel CK2 Kinase Substrates Using a Versatile Biochemical Approach

Published on: February 21, 2019

7.1K

Related Concept Videos

Targeted Cancer Therapies02:57

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...
7.0K
Inhibition of Cdk Activity02:34

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...
4.8K
M-Cdk Drives Transition Into Mitosis02:15

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...
5.3K
Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
4.4K
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
81
mTOR Signaling and Cancer Progression03:03

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...
3.6K