Related Experiment Video

Updated: Oct 4, 2025

A Robust Discovery Platform for the Identification of Novel Mediators of Melanoma Metastasis
07:41

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

Published on: March 8, 2022

2.6K

A Short Isoform of Spermatogenic Enzyme GAPDHS Functions as a Metabolic Switch and Limits Metastasis in Melanoma

Jennifer G Gill1,2, Samantha N Leef2, Vijayashree Ramesh2

  • 1University of Texas Southwestern Medical Center, Department of Dermatology, Dallas, Texas.

Cancer Research
|February 12, 2022
PubMed

Insights

A novel short isoform of glyceraldehyde-3-phosphate dehydrogenase, spermatogenic (GAPDHS) suppresses melanoma metastasis. This isoform regulates a metabolic switch from glycolysis to the tricarboxylic acid (TCA) cycle, impacting cancer cell survival.

Area of Science:

  • Oncology
  • Metabolic pathways
  • Cancer research

Background:

  • Metastasis is a complex process and the leading cause of cancer mortality.
  • Understanding metastasis regulators is crucial for developing effective cancer therapies.
  • Melanoma metastasis involves significant metabolic reprogramming.

Purpose of the Study:

  • To identify novel regulators of melanoma metastasis.
  • To characterize metabolic alterations during melanoma metastasis.
  • To investigate the role of glyceraldehyde-3-phosphate dehydrogenase, spermatogenic (GAPDHS) in melanoma metastasis and metabolism.

Main Methods:

  • RNA sequencing of patient-derived xenograft (PDX) melanoma models and their metastases.
  • Metabolomic analysis to compare primary tumors and metastases.
  • Functional studies involving GAPDHS overexpression and inhibition.
  • Isotope tracing to elucidate metabolic pathway involvement.

Main Results:

  • Melanoma metastases exhibit decreased glycolysis and increased tricarboxylic acid (TCA) cycle gene expression and metabolites compared to primary tumors.
  • A short isoform of GAPDHS was identified, downregulated in metastases, which suppresses metastasis and regulates this metabolic switch.
  • Overexpression of GAPDHS inhibited metastasis, while its inhibition promoted metastasis and altered central carbon metabolism.
  • GAPDHS influences pyruvate carboxylase activity and aspartate synthesis, critical for cancer survival.

Conclusions:

  • A short isoform of GAPDHS acts as a suppressor of melanoma metastasis.
  • GAPDHS regulates a metabolic shift critical for melanoma cell survival and metastatic potential.
  • Targeting GAPDHS or its associated metabolic pathways may offer new therapeutic strategies for melanoma.

More Related Videos

Experimental Metastasis Assay08:28

Experimental Metastasis Assay

Published on: August 24, 2010

20.4K
Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells06:09

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

Published on: June 7, 2019

9.0K

Related Concept Videos

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...
4.7K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
5.0K
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.
36.4K
GTPases and their Regulation02:14

GTPases and their Regulation

Guanine nucleotide-binding proteins (G-proteins), also known as GTPases, are a superfamily of proteins that regulate many cellular processes, such as cell signaling, vesicular transport, and the regulation of cell shape and motility. Mutation or dysfunction of these proteins can lead to disease. There are around 40,000 known G-proteins that can broadly be classified into two groups ‒  small G-proteins consisting of a single domain and large multi-domain G-proteins.
Large G-proteins,...
8.9K
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
9.5K
Activation and Inactivation of G Proteins01:22

Activation and Inactivation of G Proteins

Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high...
7.9K