Related Experiment Video

Updated: May 1, 2026

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants
07:38

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants

Published on: June 6, 2025

951

Repression of PLA2R1 by c-MYC and HIF-2alpha promotes cancer growth

David Vindrieux1, Guillaume Devailly, Arnaud Augert

  • 1Inserm U1052, Centre de Recherche en Cancérologie de Lyon, Lyon, France.

Oncotarget
|March 25, 2014
PubMed

Insights

Secreted phospholipase A2 receptor (PLA2R1) loss promotes renal cell carcinoma (RCC) growth. Oncogenic pathways involving VHL, HIF-2alpha, and c-MYC repress PLA2R1 transcription via DNA methylation, driving tumor progression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Secreted phospholipase A2 receptor (PLA2R1) exhibits tumor suppressive activities in vitro.
  • Loss of PLA2R1 confers resistance to senescence, while its overexpression induces cell cycle arrest and cancer cell death.
  • PLA2R1 expression is significantly reduced in human renal cell carcinoma (RCC).

Purpose of the Study:

  • To investigate the role of PLA2R1 in renal cell carcinoma (RCC) development.
  • To elucidate the molecular mechanisms underlying PLA2R1 downregulation in RCC.
  • To identify the oncogenic pathway responsible for PLA2R1 transcriptional repression.

Main Methods:

  • Analysis of PLA2R1 expression in human RCC samples.
  • PLA2R1 knockdown experiments in renal cancer cells to assess tumorigenicity.
  • Genetic manipulation of Von Hippel-Lindau (VHL), HIF-2alpha, and c-MYC pathways.
  • Investigation of DNA methylation patterns near the PLA2R1 transcriptional start site.

Main Results:

  • PLA2R1 expression is strongly decreased in human RCC.
  • Knockdown of PLA2R1 enhances renal cancer cell tumorigenicity in vivo.
  • Loss of VHL, stabilization of HIF-2alpha, and increased c-MYC activity lead to PLA2R1 transcriptional repression.
  • PLA2R1 repression is mediated by DNA methylation induced by the HIF-2alpha/c-MYC pathway.

Conclusions:

  • Loss of PLA2R1 contributes to RCC progression.
  • The VHL/HIF-2alpha/c-MYC pathway oncogenically represses PLA2R1 transcription through DNA methylation.
  • This study reveals a novel oncogenic mechanism driving PLA2R1 downregulation in renal cell carcinoma.

More Related Videos

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter11:32

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter

Published on: March 27, 2020

6.5K
In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice07:02

In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice

Published on: August 23, 2019

7.1K

Related Concept Videos

Induced Pluripotent Stem Cells01:06

Induced Pluripotent Stem Cells

Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic...
4.8K
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...
4.0K
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
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

1.5K
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...
6.3K
Cancer02:18

Cancer

Cancers arise due to mutations in genes involved in the regulation of cell division, which leads to unrestricted cell proliferation. Modern science and medicine have made great strides in the understanding and treatment of cancer, including eradicating cancer in some patients. However, there is still no cure for cancer. This is largely due to the fact that cancer is a large group of many diseases.
51.7K