Downregulation of RKIP is associated with poor outcome and malignant progression in gliomas

Olga Martinho1, Sara Granja, Teresa Jaraquemada

  • 1Life and Health Sciences Research Institute, Health Sciences School, University of Minho, Braga, Portugal.

Plos One
|February 1, 2012
PubMed

Insights

Absence of Raf Kinase Inhibitory protein (RKIP) in glioma tumors correlates with aggressive cancer behavior and poor patient survival. This finding suggests RKIP absence may serve as a biomarker for targeted glioma treatments.

Area of Science:

  • Neuro-oncology
  • Cancer biology
  • Molecular mechanisms of cancer

Background:

  • Malignant gliomas are aggressive, infiltrative tumors with limited treatment options.
  • Understanding glioma's molecular drivers is crucial for improving patient prognosis.
  • Raf Kinase Inhibitory protein (RKIP) impacts cancer progression and metastasis in various neoplasms, but its role in gliomas is undefined.

Purpose of the Study:

  • To investigate the expression and prognostic significance of RKIP in glioma.
  • To elucidate the functional role of RKIP in glioma cell behavior.

Main Methods:

  • Analysis of RKIP protein expression in 193 glioma tumors.
  • In vitro RKIP downregulation studies in glioma cells.
  • In vivo chick chorioallantoic membrane (CAM) assay for angiogenesis.

Main Results:

  • RKIP protein was absent in 10% of glioma tumors.
  • Absence of RKIP expression independently predicted poor prognosis in glioma patients.
  • RKIP inhibition in vitro increased glioma cell viability and migration.
  • RKIP inhibition did not affect glioma cell proliferation or angiogenesis.

Conclusions:

  • This study represents the largest evaluation of RKIP in glioma to date.
  • RKIP absence is associated with malignant glioma behavior and reduced patient survival.
  • RKIP may serve as a valuable biomarker for personalized glioma treatment strategies.

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,...
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...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...