Related Experiment Video

Updated: Jun 4, 2026

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
06:09

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells

Published on: June 7, 2019

Loss of AMBRA1 activates MAPK and angiogenesis signaling pathways in melanoma cells

Milad Ibrahim1,2, Marco Corazzari3, Iman Osman2

  • 1Faculty of Health Sciences and Wellbeing, University of Sunderland, UK.

FEBS Open Bio
|June 3, 2026
PubMed

Insights

The protein AMBRA1 is vital for autophagy and has new roles in cancer. AMBRA1 loss promotes melanoma metastasis, indicating it acts as a tumor suppressor.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Biology

Background:

  • The protein activating molecule in Beclin1-regulated autophagy1 (AMBRA1) is essential for autophagy, a cellular degradation process.
  • AMBRA1 also influences nervous system development, cell survival, and proliferation.
  • Its specific roles in cancer, particularly melanoma, require further elucidation.

Purpose of the Study:

  • To investigate the multifaceted cellular roles of AMBRA1 using a systems-based "omics" approach.
  • To identify novel pathways and binding partners associated with AMBRA1 function.
  • To determine AMBRA1's role in melanoma development and progression.

Main Methods:

  • Transcriptomic analysis was performed following AMBRA1 overexpression and knockdown.
  • Yeast two-hybrid assays were utilized to identify AMBRA1 binding partners.
  • Systems-based "omics" approaches were employed to analyze cellular processes.

Main Results:

  • AMBRA1 dysregulates numerous transcripts upon overexpression or knockdown.
  • Novel roles for AMBRA1 were identified in cancer signaling pathways (MAPK, Wnt), angiogenesis, and axon guidance.
  • New AMBRA1 binding partners were discovered, suggesting additional cellular functions.

Conclusions:

  • AMBRA1 loss leads to the upregulation of metastatic genes and proteins in melanoma.
  • AMBRA1 functions as a tumor suppressor gene in melanoma.
  • AMBRA1 plays a significant role in regulating cellular processes relevant to cancer progression.
Keywords:
AMBRA1angiogenesismelanomatumor suppressor gene

More Related Videos

Analysis of Lymph Node Volume by Ultra-High-Frequency Ultrasound Imaging in the Braf/Pten Genetically Engineered Mouse Model of Melanoma08:18

Analysis of Lymph Node Volume by Ultra-High-Frequency Ultrasound Imaging in the Braf/Pten Genetically Engineered Mouse Model of Melanoma

Published on: September 8, 2021

A Robust Discovery Platform for the Identification of Novel Mediators of Melanoma Metastasis07:41

A Robust Discovery Platform for the Identification of Novel Mediators of Melanoma Metastasis

Published on: March 8, 2022

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...
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...
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
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...
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...