KDF1, a Novel Tumor Suppressor in Clear Cell Renal Cell Carcinoma

Jing-Min Zheng1,2, Mei-Fu Gan2, Hong-Yuan Yu1

  • 1Department of Urology, Taizhou Hospital, Wenzhou Medical University, Linhai, China.

Frontiers in Oncology
|June 17, 2021
PubMed

Insights

KDF1 (Kinesis Dynamin 1) expression is reduced in clear cell renal cell carcinoma (ccRCC) and acts as a tumor suppressor. Lower KDF1 levels correlate with higher tumor grade and poorer patient survival in ccRCC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • KDF1 regulates epidermal cell proliferation and differentiation.
  • KDF1's role in renal cancer pathogenesis and its expression in clear cell renal cell carcinoma (ccRCC) remain uninvestigated.

Purpose of the Study:

  • To investigate the expression and functional significance of KDF1 in ccRCC.
  • To determine if KDF1 acts as a tumor suppressor in ccRCC.

Main Methods:

  • Immunohistochemistry and Western blot to assess KDF1 protein levels in ccRCC tissues.
  • TCGA database analysis for KDF1 mRNA expression.
  • In vitro cell experiments and allogeneic tumor transplantation to evaluate KDF1's functional impact.

Main Results:

  • KDF1 mRNA and protein expression were significantly decreased in ccRCC tissues compared to adjacent non-tumor tissues.
  • Reduced KDF1 expression correlated negatively with tumor grade and positively with patient survival.
  • KDF1 overexpression inhibited ccRCC cell proliferation, migration, and invasion, and reduced tumor growth in vivo.
  • KDF1 was identified as an independent prognostic factor for disease-specific survival in ccRCC patients.

Conclusions:

  • KDF1 is downregulated in ccRCC and functions as a tumor suppressor.
  • KDF1 holds potential as a prognostic biomarker and therapeutic target for ccRCC.

Related Concept Videos

The Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
4.3K
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...
5.1K
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
5.3K
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
8.4K
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...
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...
5.8K