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The Tumor Microenvironment

The Tumor Microenvironment

Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...

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Related Experiment Video

Updated: Dec 17, 2025

Author Spotlight: Comprehensive Epigenetic Analysis for Investigating Human Cellular Plasticity and Environmental Adaptation Using Immunofluorescence Assays

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Nuclear microenvironment in cancer: Control through liquid-liquid phase separation.

Ryu-Suke Nozawa¹, Tatsuro Yamamoto², Motoko Takahashi¹

¹Division of Experimental Pathology, The Cancer Institute of JFCR, Tokyo, Japan.

|June 29, 2020

Summary

Nuclear structures form microenvironments via liquid-liquid phase separation (LLPS). Dysregulated LLPS in cancer contributes to tumorigenesis, offering a potential therapeutic target.

Keywords:

chromatin structure intrinsically disordered region/protein liquid-liquid phase separation non-coding RNA nuclear microenvironment

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Area of Science:

Cell Biology
Biophysics
Cancer Biology

Background:

The eukaryotic nucleus contains diverse membraneless structures (e.g., nucleoli, PML bodies) that create specific microenvironments.
Altered nuclear structures are observed in cancers, contributing to nuclear atypia, but their underlying mechanisms are unclear.

Purpose of the Study:

To review the biophysical principles of liquid-liquid phase separation (LLPS) governing nuclear biomolecular condensate assembly.
To explore the role of LLPS in nuclear microenvironment formation and its implications in cancer.

Main Methods:

Review of emerging biophysical principles of LLPS in the nucleus.
Discussion of LLPS drivers, including protein-nucleic acid interactions and intrinsically disordered regions.
Analysis of the link between altered LLPS, nuclear events, epigenetics, and tumorigenesis.

Main Results:

LLPS is a key biophysical mechanism driving the formation of nuclear membraneless structures.
LLPS is typically driven by multivalent interactions and facilitated by non-coding RNAs.
Altered LLPS is implicated in epigenetic dysregulation, cancer development, and progression.

Conclusions:

LLPS provides a framework for understanding nuclear microenvironments and their role in biological processes.
Dysregulation of LLPS is a significant factor in tumorigenesis and cancer progression.
Targeting LLPS presents a potential novel therapeutic strategy for cancer intervention.