Related Experiment Video

Updated: Mar 7, 2026

A Syngeneic Mouse Model of Metastatic Renal Cell Carcinoma for Quantitative and Longitudinal Assessment of Preclinical Therapies
06:38

A Syngeneic Mouse Model of Metastatic Renal Cell Carcinoma for Quantitative and Longitudinal Assessment of Preclinical Therapies

Published on: April 12, 2017

14.3K

Upregulation of MARCKS in kidney cancer and its potential as a therapeutic target

C-H Chen1,2, L W R Fong3, E Yu1,4

  • 1Division of Nephrology, Department of Internal Medicine, University of California Davis, Davis, CA, USA.

Oncogene
|February 7, 2017
PubMed

Insights

Myristoylated alanine-rich C kinase substrate (MARCKS) drives kidney cancer growth and resistance to targeted therapies. Suppressing MARCKS may improve treatment efficacy for renal cell carcinoma (RCC).

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Targeted therapies for renal cell carcinoma (RCC), including those inhibiting hypoxia-inducible factor (HIF)/vascular endothelial growth factor (VEGF) signaling, often face drug resistance.
  • Resistance mechanisms frequently involve the activation of alternative signaling pathways.
  • Identifying novel therapeutic targets is crucial for overcoming resistance in kidney cancer.

Purpose of the Study:

  • To investigate the role of myristoylated alanine-rich C kinase substrate (MARCKS) in kidney cancer progression and therapeutic resistance.
  • To explore MARCKS as a potential therapeutic target for renal cell carcinoma (RCC).

Main Methods:

  • Genome-scale integrated analysis of the HIF-α network to identify potential targets.
  • Screening of 56 RCC patient samples for MARCKS expression and phosphorylation.
  • In vitro and in vivo experiments using RCC cell lines and xenografts to assess the effects of MARCKS suppression.
  • Investigating the interaction between MARCKS, AKT/mTOR pathway, and HIF-target genes.
  • Evaluating the synergistic effect of MARCKS inhibition with regorafenib.

Main Results:

  • MARCKS expression and phosphorylation are elevated in high-grade RCC and correlate with tumor grade.
  • Suppression of MARCKS reduced proliferation and migration in vitro and inhibited tumor growth and angiogenesis in vivo.
  • MARCKS acts upstream of the AKT/mTOR pathway, influencing HIF-target genes like VEGF-A.
  • MARCKS knockdown decreased the IC50 of regorafenib, and its attenuation synergized with regorafenib to reduce cancer cell survival.

Conclusions:

  • MARCKS plays a significant role in kidney cancer growth, angiogenesis, and resistance to targeted therapies.
  • Targeting MARCKS presents a promising strategy to enhance the efficacy of existing multikinase inhibitors in RCC treatment.
  • Further investigation into MARCKS as a therapeutic target could lead to improved outcomes for kidney cancer patients.

More Related Videos

Modeling Spontaneous Metastatic Renal Cell Carcinoma mRCC in Mice Following Nephrectomy11:27

Modeling Spontaneous Metastatic Renal Cell Carcinoma mRCC in Mice Following Nephrectomy

Published on: April 29, 2014

17.3K
Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts10:27

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts

Published on: July 25, 2020

8.0K

Related Concept Videos

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...
5.0K
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...
9.0K
Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which...
10.8K
Mitogens and the Cell Cycle02:38

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...
8.2K
Abnormal Proliferation02:23

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...
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:
4.6K