Related Experiment Video

Updated: May 16, 2026

RhoC GTPase Activation Assay
09:58

RhoC GTPase Activation Assay

Published on: August 22, 2010

A novel interplay between Rap1 and PKA regulates induction of angiogenesis in prostate cancer

Jyotsana Menon1, Robert C Doebele, Suzana Gomes

  • 1Ben May Department for Cancer Research, The University of Chicago, Chicago, Illinois, United States of America.

Plos One
|November 21, 2012
PubMed

Insights

Stimulating protein kinase A (PKA) with 8-pCPT-2'-O-Me-cAMP (8CPT) inhibits prostate tumor growth and angiogenesis. This occurs by PKA antagonizing the Epac/Rap1 pathway, revealing a novel therapeutic target for advanced prostate cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Angiogenesis inhibition is a key strategy for treating advanced prostate cancer.
  • Previous studies indicated Rap1 activation suppresses endothelial cell chemotaxis and angiogenesis.

Purpose of the Study:

  • To investigate the therapeutic potential of Rap1 modulation in prostate cancer.
  • To elucidate the underlying molecular mechanisms of angiogenesis regulation in prostate tumors.

Main Methods:

  • Utilized a prostate tumor xenograft model.
  • Administered 8-pCPT-2 -O-Me-cAMP (8CPT) and analyzed tumor growth, VEGF expression, and angiogenesis.
  • Investigated the roles of Epac, Rap1, and protein kinase A (PKA) pathways.

Main Results:

  • 8CPT alone did not significantly affect tumor growth.
  • In xenografts with constitutively active Rap1 (cRap1), 8CPT inhibited tumor growth, VEGF expression, and angiogenesis.
  • In prostate tumor cells, 8CPT stimulated PKA, which antagonized Epac/Rap1 signaling and hypoxic induction of angiogenesis.

Conclusions:

  • A novel interplay between Rap1, Epac, and PKA regulates tumor-stromal angiogenesis.
  • PKA activation represents a potential therapeutic strategy for inhibiting prostate tumor growth and angiogenesis.

More Related Videos

Development and Application of Rapamycin-regulated Tyrosine Phosphatases06:56

Development and Application of Rapamycin-regulated Tyrosine Phosphatases

Published on: September 6, 2024

Identification of Inositol Phosphate or Phosphoinositide Interacting Proteins by Affinity Chromatography Coupled to Western Blot or Mass Spectrometry08:07

Identification of Inositol Phosphate or Phosphoinositide Interacting Proteins by Affinity Chromatography Coupled to Western Blot or Mass Spectrometry

Published on: July 26, 2019

Related Concept Videos

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...
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...
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...
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...
Mechanism of Angiogenesis01:10

Mechanism of Angiogenesis

Blood vessel formation starts early during embryonic development, around day 7. In the extraembryonic yolk sac, mesodermal precursor cells called hemangioblast proliferate and differentiate into angioblast. Angioblasts express vascular endothelial growth factor receptor 2 or VEGFR2, which binds VEGF-A, a proangiogenic factor, guiding blood vessel formation. VEGF signaling promotes angioblasts to form a blood island in the developing embryo. Angioblasts further differentiate, giving rise to...
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...