Related Experiment Video

Updated: Dec 28, 2025

Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome
07:23

Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome

Published on: June 15, 2016

8.8K

Unphosphorylated STAT3 in heterochromatin formation and tumor suppression in lung cancer

Pranabananda Dutta1, Lin Zhang1, Huijun Zhang1,2

  • 1Department of Medicine, University of California San Diego, La Jolla, CA, 92093, USA.

BMC Cancer
|February 24, 2020
PubMed
Abstract

Insights

Unphosphorylated STAT3 (uSTAT3) promotes heterochromatin formation, suppressing lung cancer cell proliferation and tumor growth. This non-canonical function reveals STAT3

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Aberrant Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) pathway activation is implicated in human cancers.
  • While phosphorylated STAT (pSTAT) directly regulates gene expression, unphosphorylated STAT (uSTAT) was traditionally considered cytoplasmic and inactive.
  • Emerging evidence suggests nuclear localization and tumor suppressor roles for uSTATs, but a unifying mechanism is lacking.

Purpose of the Study:

  • To investigate the role of unphosphorylated STAT3 (uSTAT3) in lung cancer development.
  • To elucidate the non-canonical functions of STAT3 in cancer biology.

Main Methods:

  • Utilized a combination of advanced imaging techniques.
  • Employed cell biological assays for in vitro analysis.
  • Validated findings using mouse xenograft models.

Main Results:

  • Unphosphorylated STAT3 (uSTAT3) was found to actively promote heterochromatin formation in lung cancer cells.
  • uSTAT3 demonstrated potent suppression of cancer cell proliferation in vitro.
  • Tumor growth was significantly suppressed in mouse xenografts when uSTAT3 function was present.

Conclusions:

  • Unphosphorylated STAT3 (uSTAT3) exhibits a non-canonical function in promoting heterochromatin formation.
  • The tumor suppressor activity of STAT3 is likely mediated by its heterochromatin-promoting role within the non-canonical JAK/STAT pathway.
Keywords:
FRETHeterochromatinJAK/STATLung cancerUSTAT3

More Related Videos

Merging Absolute and Relative Quantitative PCR Data to Quantify STAT3 Splice Variant Transcripts11:19

Merging Absolute and Relative Quantitative PCR Data to Quantify STAT3 Splice Variant Transcripts

Published on: October 9, 2016

15.4K
Author Spotlight: Exploring the Role of Inflammation in the Co-occurrence of Primary Sjogren's Syndrome and Lung Adenocarcinoma10:21

Author Spotlight: Exploring the Role of Inflammation in the Co-occurrence of Primary Sjogren's Syndrome and Lung Adenocarcinoma

Published on: September 20, 2024

679

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...
11.6K
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...
5.0K
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
5.7K
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...
4.5K
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
9.3K
Epigenetic Regulation01:37

Epigenetic Regulation

Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
3.6K