Related Experiment Video

Updated: May 22, 2026

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer
06:51

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer

Published on: July 21, 2018

Inactivation of Spry2 accelerates AKT-driven hepatocarcinogenesis via activation of MAPK and PKM2 pathways

Chunmei Wang1, Salvatore Delogu, Coral Ho

  • 1Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA 94143, USA.

Journal of Hepatology
|May 24, 2012
PubMed
Abstract

Insights

Loss of Sprouty 2 (Spry2) accelerates AKT-driven liver cancer by activating MAPK and PKM2 pathways. This study reveals a key molecular mechanism in hepatocarcinogenesis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Hepatology

Background:

  • Aberrant AKT pathway activation and Sprouty 2 (Spry2) downregulation are hallmarks of human hepatocarcinogenesis.
  • Investigating the crosstalk between AKT and Spry2 is crucial for understanding liver cancer development.

Purpose of the Study:

  • To elucidate the biochemical and genetic interactions between activated AKT and Spry2 inactivation in liver cancer.
  • To determine the role of Spry2 loss in AKT-driven hepatocarcinogenesis using in vivo and in vitro models.

Main Methods:

  • Overexpression of activated AKT and a dominant-negative Spry2 mutant (Spry2Y55F) in mouse liver via hydrodynamic gene delivery.
  • Histological and biochemical analyses of liver tumors to characterize molecular features.
  • In vitro studies using HCC cell lines to investigate molecular mechanisms of Spry2 loss-driven cancer.

Main Results:

  • Spry2Y55F overexpression accelerated AKT-induced hepatocarcinogenesis, increasing proliferation and glycolysis while decreasing lipogenesis.
  • AKT/Spry2Y55F tumors showed enhanced activation of mitogen-activated protein kinase (MAPK) and pyruvate kinase M2 (PKM2) pathways.
  • Suppression of MAPK and PKM2 pathways significantly inhibited tumor growth in AKT-overexpressing cells.

Conclusions:

  • Spry2 inactivation promotes AKT-induced liver cancer progression.
  • The activation of MAPK and PKM2 pathways is a key mechanism by which Spry2 loss drives hepatocarcinogenesis.

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...
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...
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...
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...
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...
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...