Related Experiment Video

Updated: May 11, 2026

Modeling Oral-Esophageal Squamous Cell Carcinoma in 3D Organoids
10:43

Modeling Oral-Esophageal Squamous Cell Carcinoma in 3D Organoids

Published on: December 23, 2022

Acylglycerol kinase augments JAK2/STAT3 signaling in esophageal squamous cells

Xiuting Chen1, Zhe Ying, Xi Lin

  • 1State Key Laboratory of Oncology in Southern China, Department of Experimental Research, Cancer Center, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.

The Journal of Clinical Investigation
|May 17, 2013
PubMed

Insights

AGK protein overexpression activates JAK2/STAT3 signaling in solid tumors by inhibiting the JAK homology domain 2 (JH2) of JAK2. This promotes cancer stem cells and tumorigenicity, offering a potential therapeutic target.

Area of Science:

  • Molecular Biology
  • Oncology
  • Signal Transduction

Background:

  • Janus kinase 2 (JAK2) activity is regulated by its JAK homology domain 2 (JH2) to control JAK2/STAT3 signaling.
  • Mutations in JAK2 are common in hematological malignancies but not solid tumors, leaving the mechanism of JAK2/STAT3 activation in solid tumors unclear.

Purpose of the Study:

  • To investigate the mechanism by which solid tumors achieve constitutive JAK2/STAT3 activation.
  • To identify potential biomarkers and therapeutic targets for solid tumors driven by JAK2/STAT3 hyperactivation.

Main Methods:

  • Investigated the interaction between AGK and the JH2 domain of JAK2.
  • Assessed the effect of AGK overexpression on JAK2/STAT3 signaling, cancer stem cell populations, and tumorigenicity in esophageal squamous cell carcinoma (ESCC) cells in vitro and in vivo.
  • Correlated AGK levels with STAT3 phosphorylation, patient survival, and JAK2/STAT3 hyperactivation in primary ESCC, lung, and breast cancer tissues.

Main Results:

  • AGK directly interacts with the JAK2 JH2 domain, relieving its inhibitory effect and activating JAK2/STAT3 signaling.
  • AGK overexpression sustains JAK2/STAT3 activation, enhances cancer stem cell populations, and augments tumorigenicity in ESCC.
  • Elevated AGK levels correlate with increased STAT3 phosphorylation, reduced disease-free and overall survival in ESCC, and JAK2/STAT3 hyperactivation across ESCC, lung, and breast cancers.

Conclusions:

  • AGK is a novel mechanism for constitutive JAK2/STAT3 activation in solid tumors.
  • AGK represents a potential prognostic biomarker and therapeutic target for solid tumors exhibiting JAK2/STAT3 hyperactivation.

More Related Videos

An Immunofluorescent Method for Characterization of Barrett’s Esophagus Cells08:54

An Immunofluorescent Method for Characterization of Barrett’s Esophagus Cells

Published on: July 20, 2014

Related Concept Videos

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...
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze 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...
Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
Two...
cAMP-dependent Protein Kinase Pathways01:25

cAMP-dependent Protein Kinase Pathways

Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...