Related Experiment Video

Updated: Jun 4, 2026

Real-time Imaging of Myeloid Cells Dynamics in ApcMin/+ Intestinal Tumors by Spinning Disk Confocal Microscopy
05:21

Real-time Imaging of Myeloid Cells Dynamics in ApcMin/+ Intestinal Tumors by Spinning Disk Confocal Microscopy

Published on: October 6, 2014

JNK signaling promotes intestinal tumorigenesis through activation of mTOR complex 1 in Apc(Δ716) mice

Teruaki Fujishita1, Masahiro Aoki, Makoto M Taketo

  • 1Department of Pharmacology, Graduate School of Medicine, Kyoto University, Yoshida-Konoé-Cho, Sakyo-Ku, Kyoto, Japan.

Gastroenterology
|February 16, 2011
PubMed
Abstract

Insights

C-Jun-NH(2)-terminal kinase (JNK) activates mammalian target of rapamycin complex 1 (mTORC1) signaling in intestinal tumors. Inhibiting JNK may prevent tumor formation and serve as a therapeutic strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Mammalian target of rapamycin complex 1 (mTORC1) signaling is linked to human cancers.
  • mTORC1 is activated in intestinal tumors of Apc(Δ716) mice, and its inhibition blocks tumor formation.
  • The exact mechanism of mTORC1 activation in intestinal tumors remains unclear.

Purpose of the Study:

  • To investigate the role of c-Jun-NH(2)-terminal kinase (JNK) in mTORC1 activation within intestinal tumors.
  • To explore potential therapeutic strategies targeting JNK for intestinal tumor prevention.

Main Methods:

  • Examined the effects of JNK inhibitors, activators, and small interfering RNA (siRNA) against JNK on mTORC1 signaling in Apc(Δ716) mice and colon cancer cell lines.
  • Utilized in vitro kinase assays to determine JNK's role in mTORC1 activation.

Main Results:

  • JNK was activated in intestinal polyps of Apc(Δ716) mice, and JNK inhibition suppressed tumor formation.
  • In colorectal cancer cell lines, JNK activation led to mTORC1 activation, while JNK inhibition suppressed it.
  • JNK directly phosphorylated Raptor at serine 863, stimulating mTORC1 kinase activity.

Conclusions:

  • JNK is essential for activating mTORC1 in intestinal tumor cells.
  • JNK inhibitors show potential as therapeutics for intestinal tumors or for preventing their development.

More Related Videos

Tumor Allotransplantation in Drosophila melanogaster with a Programmable Auto-Nanoliter Injector05:06

Tumor Allotransplantation in Drosophila melanogaster with a Programmable Auto-Nanoliter Injector

Published on: February 2, 2021

Protocols for Analyzing the Role of Paneth Cells in Regenerating the Murine Intestine using Conditional Cre-lox Mouse Models07:48

Protocols for Analyzing the Role of Paneth Cells in Regenerating the Murine Intestine using Conditional Cre-lox Mouse Models

Published on: November 21, 2015

Related Concept Videos

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