Related Experiment Video

Updated: May 30, 2025

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
06:54

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

12.8K

Dense stroma activates the TGF-β1/FBW7 axis to induce metabolic subtype switching in pancreatic cancer

Zeyin Rong1,2,3,4, Jianhui Yang1,2,3,4, Jiang Liu1,2,3,4

  • 1Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.

International Journal of Surgery (London, England)
|January 27, 2025
PubMed
Abstract

Insights

Pancreatic cancer (PDAC) can be classified into glycolytic and lipogenic subtypes. The TGF-β1/FBW7 ratio identifies these subtypes and predicts patient prognosis and gemcitabine resistance.

Area of Science:

  • Oncology
  • Metabolic Research
  • Cancer Biology

Background:

  • Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal malignancy.
  • Limited targeted therapies have improved survival due to viewing PDAC as a single disease.

Purpose of the Study:

  • To stratify PDAC into distinct metabolic subtypes.
  • To investigate the role of TGF-β1/FBW7 in metabolic switching.
  • To identify a molecular marker for gemcitabine resistance in PDAC.

Main Methods:

  • Metabolomic analysis, immunohistochemistry, and Oil Red O staining.
  • Oxygen consumption and extracellular acidification rate measurements.
  • In vitro and in vivo validation of TGF-β1/FBW7 signaling.
  • Cell growth assays to determine gemcitabine resistance markers.

Main Results:

  • PDAC was stratified into glycolytic and lipogenic subtypes.
  • TGF-β1 (from fibroblasts) and FBW7 (from tumor cells) co-determine metabolic phenotypes.
  • A high TGF-β1/FBW7 ratio indicates glycolytic PDAC with dense stroma, mesenchymal features, and poor prognosis.
  • Glycolytic PDAC showed sensitivity to gemcitabine and TGF-βR1 inhibitor combination therapy.

Conclusions:

  • The TGF-β1/FBW7 ratio serves as a molecular marker for PDAC metabolic phenotypes.
  • This marker may aid in developing targeted therapies to improve PDAC patient survival.

More Related Videos

Author Spotlight: Validating Cancer Therapy Responses with Desmoplastic Spheroid Models03:42

Author Spotlight: Validating Cancer Therapy Responses with Desmoplastic Spheroid Models

Published on: September 27, 2024

1.3K
Author Spotlight: Semi-Automated Isolation of the Stromal Vascular Fraction from Murine White Adipose Tissue Using a Tissue Dissociator06:08

Author Spotlight: Semi-Automated Isolation of the Stromal Vascular Fraction from Murine White Adipose Tissue Using a Tissue Dissociator

Published on: May 19, 2023

2.0K

Related Concept Videos

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...
7.2K
The Tumor Microenvironment02:17

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...
6.5K
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...
3.7K
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...
3.4K