Related Experiment Video

Updated: Nov 10, 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

13.7K

Type III TGF-β Receptor Down-Regulation Promoted Tumor Progression via Complement Component C5a Induction in

Oscar Wai Ho Yeung1, Xiang Qi1, Li Pang1

  • 1Department of Surgery, HKU-SZH & The University of Hong Kong, Pokfulam, Hong Kong SAR, China.

Cancers
|April 3, 2021
PubMed

Insights

Transforming growth factor-beta receptor type III (TGFβR3) downregulation promotes hepatocellular carcinoma (HCC) progression. Reduced TGFβR3 levels correlate with poor HCC prognosis by increasing complement C5a, which fuels tumor growth.

Area of Science:

  • Oncology
  • Molecular Biology
  • Immunology

Background:

  • Transforming growth factor-beta (TGF-β) signaling is crucial in tumorigenesis.
  • TGF-β receptor type III (TGFβR3) is notably underexpressed in many cancers.
  • The role of TGFβR3 in hepatocellular carcinoma (HCC) remains poorly understood.

Purpose of the Study:

  • To investigate the clinical impact of TGFβR3 downregulation in HCC.
  • To elucidate the underlying mechanisms by which reduced TGFβR3 expression promotes HCC progression.

Main Methods:

  • Quantified TGFβR3 and soluble TGFβR3 (sTGFβR3) in 100 HCC patients' plasma and liver tissues using qPCR and ELISA.
  • Utilized HCC mouse models and TGFβR3 knockout cell lines to study molecular mechanisms.
  • Assessed complement component C5a levels and Th-17 immune responses.

Main Results:

  • Significantly lower TGFβR3 and sTGFβR3 levels were observed in HCC patients compared to healthy controls (p < 0.01).
  • Low sTGFβR3 (<9.4 ng/mL) correlated with advanced tumor stage, higher recurrence, and shorter disease-free survival (p < 0.05).
  • TGFβR3 deficiency led to increased complement C5a, which activated pro-tumorigenic Th-17 responses in macrophages, correlating with poor prognosis (p < 0.01).

Conclusions:

  • TGFβR3 acts as a tumor suppressor in HCC progression.
  • Decreased TGFβR3 expression is linked to poor HCC prognosis.
  • Upregulation of complement C5a by reduced TGFβR3 drives HCC tumor growth and adverse outcomes.
Keywords:
clinical outcomescomplement componentdiagnosis predictiontherapeutic potentialtumor-suppressive protein

More Related Videos

Spheroid Assay to Measure TGF-&#946;-induced Invasion09:18

Spheroid Assay to Measure TGF-β-induced Invasion

Published on: November 16, 2011

22.2K
An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis06:38

An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis

Published on: September 12, 2019

9.2K

Related Concept Videos

TGF - &#946; 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...
8.2K
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR...
2.5K
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
3.0K
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...
7.2K