Related Experiment Video

Updated: Sep 4, 2026

Gene Regulation and Targeted Therapy in Gastric Cancer Peritoneal Metastasis: Radiological Findings from Dual Energy CT and PET/CT
10:28

Gene Regulation and Targeted Therapy in Gastric Cancer Peritoneal Metastasis: Radiological Findings from Dual Energy CT and PET/CT

Published on: January 22, 2018

11.4K

TFF1 activates p53 through down-regulation of miR-504 in gastric cancer

Mohammed Soutto1, Zheng Chen2, Mohamed A Saleh3

  • 1Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, Tennessee, USA. Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, USA.

Oncotarget
|July 13, 2014
PubMed

Insights

Trefoil factor 1 (TFF1) suppresses gastric cancer growth by activating p53. TFF1 achieves this by down-regulating miR-504, a key inhibitor of p53, revealing a novel tumor suppressor mechanism.

Area of Science:

  • Oncology
  • Molecular Biology
  • Gene Regulation

Background:

  • TFF1 expression is reduced in human gastric cancer, and its absence promotes tumor development in mice.
  • The precise molecular mechanisms of TFF1's tumor suppressor activity are not fully understood.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which TFF1 exerts its tumor suppressor functions in gastric cancer.
  • To investigate the role of TFF1 in regulating cell growth, cell death, and p53 activity in gastric cancer models.

Main Methods:

  • In vitro studies utilized colony formation assays and Annexin V staining to assess cell growth and death.
  • In vivo studies employed a gastric cancer xenograft mouse model to evaluate tumor growth suppression.
  • Molecular analyses included luciferase reporter assays, Western blotting, protein stability assays, and quantitative real-time PCR to examine TFF1, p53, and miR-504 interactions.

Main Results:

  • Reconstitution of TFF1 expression inhibited gastric cancer cell growth and induced cell death in vitro.
  • TFF1 suppressed tumor growth in a gastric cancer xenograft mouse model.
  • TFF1 enhanced p53 expression and transcriptional activity, independent of p53 mRNA levels or protein stability.
  • TFF1 was found to down-regulate miR-504, a known negative regulator of p53.
  • miR-504 was shown to counteract TFF1-mediated p53 activation.

Conclusions:

  • TFF1 functions as a tumor suppressor in gastric cancer by activating p53.
  • This activation is mediated through the down-regulation of miR-504, a novel mechanism for TFF1's tumor suppressor activity.
  • These findings provide new insights into gastric cancer pathogenesis and potential therapeutic targets.

More Related Videos

Author Spotlight: Unveiling Transmembrane Protein Family-Related Markers in Gastric Cancer and Implications for Targeted Therapies07:47

Author Spotlight: Unveiling Transmembrane Protein Family-Related Markers in Gastric Cancer and Implications for Targeted Therapies

Published on: September 15, 2023

2.0K
Author Spotlight: Genetic Profiling for Fluorouracil Response in Gastric Cancer06:21

Author Spotlight: Genetic Profiling for Fluorouracil Response in Gastric Cancer

Published on: May 10, 2024

1.1K

Related Concept Videos

Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
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 daughter...
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...
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...
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...
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...