Related Experiment Video

Updated: Jun 30, 2025

Advanced Animal Model of Colorectal Metastasis in Liver: Imaging Techniques and Properties of Metastatic Clones
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Advanced Animal Model of Colorectal Metastasis in Liver: Imaging Techniques and Properties of Metastatic Clones

Published on: November 30, 2016

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Cancer Cells Hijack Physiologic Metabolic Signals to Seed Liver Metastasis

Andres R Rettig1, Karuna Ganesh1,2

  • 1Molecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York.

Cancer Research
|March 19, 2024
PubMed

Insights

Researchers found Pip4k2c drives liver metastasis by enhancing insulin signaling in cancer cells. This process can be reversed through specific drug combinations or a ketogenic diet, offering new therapeutic avenues.

Area of Science:

  • Oncology
  • Cancer Biology
  • Metabolism

Background:

  • Metastasis, the spread of cancer, is influenced by cancer cell adaptations and the tumor microenvironment (TME).
  • Understanding organ-specific metastasis (organotropism) is crucial for developing targeted cancer therapies.
  • The TME's interaction with systemic physiology significantly impacts cancer progression.

Purpose of the Study:

  • To identify key molecular drivers of liver metastasis.
  • To elucidate the mechanisms by which cancer cells adapt to specific organ environments.
  • To explore potential therapeutic strategies targeting organotropism.

Main Methods:

  • Identification of Pip4k2c as a critical factor in liver metastasis.
  • Investigation of Pip4k2c's role in mediating insulin-dependent phosphoinositide 3-kinase/AKT (PI3K/AKT) signaling.
  • Evaluation of therapeutic interventions including dual PI3K/SGLT2 inhibition and ketogenic diet.

Main Results:

  • Pip4k2c was identified as a driver of liver metastasis.
  • Pip4k2c sensitizes cancer cells to insulin-dependent PI3K/AKT signaling.
  • Dual inhibition of PI3K and SGLT2, or a ketogenic diet, reversed the pro-metastatic effects.

Conclusions:

  • Pip4k2c plays a significant role in liver metastasis by modulating cancer cell signaling.
  • Targeting metabolic pathways and signaling cascades presents a promising strategy for preventing or treating liver metastasis.
  • The study underscores the importance of systemic physiology in cancer progression and highlights potential combination therapies.

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