Related Experiment Video

Updated: Jan 9, 2026

Merging Absolute and Relative Quantitative PCR Data to Quantify STAT3 Splice Variant Transcripts
11:19

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

Published on: October 9, 2016

15.4K

A hyperactive splice variant of STAT3 promotes colonic inflammation-associated tumorigenesis in mice

Meng Xu1, Dingju Wei1, Shu Zhong1

  • 1Key Laboratory of Pesticide & Chemical Biology of Ministry of Education, Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan, China.

Science Translational Medicine
|December 10, 2025
PubMed

Insights

Signal transducer and activator of transcription 3 (STAT3) isoforms, generated by cryptic splice sites, impact colon cancer. The absence of Ser701 in STAT3 promotes inflammation and tumorigenesis.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Cancer Research

Background:

  • Signal transducer and activator of transcription 3 (STAT3) is crucial for cell signaling.
  • STAT3 overactivation is linked to inflammation and cancer.
  • Mechanisms regulating STAT3 in disease are not fully understood.

Purpose of the Study:

  • Investigate the role of STAT3 heterogeneity in colon cancer.
  • Elucidate the mechanisms of STAT3 regulation by phosphorylation and splicing.

Main Methods:

  • Analysis of STAT3 isoforms (wS701/ΔS701) in colon cancer.
  • Studied phosphorylation of Ser701 (p-S701) and its regulation by mTORC1 and PP2A.
  • Utilized mouse models with STAT3 S701 deletion.

Main Results:

  • Cryptic splice sites in STAT3 create isoforms differing by Ser701.
  • STAT3_ΔS701 isoform is more abundant in colon cancers and is hyperactive.
  • Phosphorylation at S701 (p-S701) acts as a self-restricting mechanism for STAT3 activity.
  • S701 deletion in mice increases susceptibility to colonic inflammation and tumorigenesis.
  • PP2A inhibition alleviates colon inflammation in wild-type mice by sustaining p-S701.

Conclusions:

  • STAT3 heterogeneity, specifically the presence or absence of Ser701, is critical in colonic inflammation and colorectal cancer.
  • The STAT3 self-restricting mechanism involving S701 phosphorylation is vital for preventing pathological STAT3 activation.

More Related Videos

A Genetically Engineered Mouse Model of Sporadic Colorectal Cancer06:01

A Genetically Engineered Mouse Model of Sporadic Colorectal Cancer

Published on: July 6, 2017

9.9K
Skeletal Phenotype Analysis of a Conditional Stat3 Deletion Mouse Model08:42

Skeletal Phenotype Analysis of a Conditional Stat3 Deletion Mouse Model

Published on: July 3, 2020

5.0K

Related Concept Videos

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...
5.3K
RNA Splicing01:32

RNA Splicing

Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...
60.2K
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...
2.4K
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...
11.8K
Induced Pluripotent Stem Cells01:06

Induced Pluripotent Stem Cells

Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic...
5.3K
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...
5.1K