Related Experiment Video

Updated: Jun 3, 2026

Exploring the Effects of Spaceflight on Mouse Physiology using the Open Access NASA GeneLab Platform
11:08

Exploring the Effects of Spaceflight on Mouse Physiology using the Open Access NASA GeneLab Platform

Published on: January 13, 2019

Attenuated expression and function of the RECK tumor suppressor under hypoxic conditions is mediated by the MAPK

Hye Won Jeon1, Kyung-Ju Lee, Sun Hee Lee

  • 1School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University, Daegu, Korea.

Archives of Pharmacal Research
|April 7, 2011
PubMed

Insights

Hypoxia downregulates the tumor suppressor RECK (reversion-inducing cysteine-rich protein with Kazal motifs) via ERK, JNK, and p38 MAPK pathways, indirectly affecting cancer cell migration and MMP activity.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Signaling

Background:

  • The tumor suppressor RECK (reversion-inducing cysteine-rich protein with Kazal motifs) is downregulated under hypoxic conditions.
  • The specific signaling pathways mediating RECK downregulation by hypoxia remain unidentified.

Purpose of the Study:

  • To elucidate the signaling pathways involved in hypoxia-induced RECK downregulation.
  • To investigate the role of MAPK pathways in RECK suppression and its downstream effects on cancer cell behavior.

Main Methods:

  • Semiquantitative RT-PCR and RECK promoter luciferase assays were used to analyze RECK mRNA expression and promoter activity.
  • Western blotting assessed MAPK phosphorylation, while zymography evaluated matrix metalloproteinase (MMP) activity.
  • Cell migration assays and DNA precipitation assays were employed to study cancer cell migration and HIF-1α binding.

Main Results:

  • Hypoxia suppressed RECK mRNA expression, which was reversed by inhibiting ERK, JNK, and p38 MAPK pathways.
  • Hypoxia increased phosphorylation of ERK, JNK, and p38 MAPKs, and elevated MMP-2 and MMP-9 activities.
  • Inhibiting these MAPK pathways blocked hypoxia-induced cancer cell migration and did not affect HIF-1α binding to the RECK promoter.

Conclusions:

  • ERK, JNK, and p38 MAPK signaling pathways are indirectly involved in hypoxia-induced RECK suppression.
  • These pathways mediate RECK downregulation independently of HIF-1α's direct binding to the RECK promoter, influencing cancer cell migration and MMP activity.

More Related Videos

Co-immunoprecipitation Assay Using Endogenous Nuclear Proteins from Cells Cultured Under Hypoxic Conditions09:17

Co-immunoprecipitation Assay Using Endogenous Nuclear Proteins from Cells Cultured Under Hypoxic Conditions

Published on: August 2, 2018

Related Concept Videos

MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
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...
Adaptive Mechanisms in Cancer Cells02:53

Adaptive Mechanisms in Cancer Cells

Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
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 daughter...