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TGF beta Signaling Pathway – Cancer, Fibrosis and Biomarker Analysis

What is the TGF beta signaling pathway

The TGF beta signaling pathway (Transforming Growth Factor beta signaling pathway) is a fundamental regulator of cell growth, differentiation, immune homeostasis, and tissue remodeling. It plays a dual role in physiology and disease by tightly controlling cellular plasticity, inflammation, and extracellular matrix production.

TGF-β signaling is activated in response to developmental cues, tissue injury, and immune challenges. Depending on cellular context, it can suppress cell proliferation and inflammation or promote fibrosis, immune evasion, and tumor progression.

Dysregulation of the TGF beta signaling pathway is a hallmark of cancer progression, fibrotic disorders, and immune-mediated diseases, making it a major focus of translational research and therapeutic development.

AnyGenes® TGF beta Signaling Pathway Array for Gene Expression Analysis.

TGF beta signaling pathway activity can be efficiently assessed by measuring gene expression of core regulators, downstream targets, and pathway-specific biomarker signatures.

TGF beta signaling pathway biomarker list
View the genes included in our TGF-β pathway qPCR arrays.

TGF-beta-signaling- pathway-branches
Overview of the TGFβ family pathways.

Key takeaways

  • Central regulator of cell fate, differentiation, and tissue remodeling
  • Operates through canonical SMAD and non-canonical signaling branches
  • Critical driver of fibrosis, EMT, and tumor progression
  • Major immunomodulatory pathway in cancer and autoimmunity
  • Highly suitable for biomarker discovery and gene expression profiling

Core components of the TGF beta signaling pathway

TGF-β ligands

The TGF-β superfamily includes TGF-β1, TGF-β2, and TGF-β3, as well as activins and bone morphogenetic proteins (BMPs), which regulate development and tissue homeostasis.

TGF-β receptors

TGF-β signals through type I (TGFBR1) and type II (TGFBR2) serine/threonine kinase receptors. Ligand binding triggers receptor complex formation and downstream signaling activation.

SMAD transcription factors

Canonical signaling is mediated by SMAD2 and SMAD3, which associate with SMAD4 and translocate to the nucleus to regulate gene expression.

Regulatory proteins

Inhibitory SMADs (SMAD6, SMAD7) and co-factors fine-tune pathway intensity and duration, preventing excessive signaling.

Mechanisms of TGF beta signaling

TGF-β signaling operates through two major branches:

Canonical (SMAD-dependent) signaling

  • Activation of SMAD2/3 phosphorylation
  • Formation of SMAD2/3-SMAD4 complexes
  • Nuclear translocation and transcriptional regulation of target genes

Non-canonical (SMAD-independent) signaling

The integration of these branches allows TGF-β to exert context-dependent effects on cell fate and immune responses.

Biological functions of the TGF beta pathway

TGF-β signaling regulates:

TGF beta signaling pathway in disease

Cancer

TGF-β acts as a tumor suppressor in early stages but promotes invasion, metastasis, immune evasion, and cancer stemness in advanced tumors.

Fibrosis

Persistent activation drives excessive collagen deposition and tissue scarring in organs such as lung, liver, kidney, and heart.

Immune-mediated disorders

TGF-β modulates immune tolerance and inflammation, contributing to autoimmune diseases and tumor-associated immunosuppression.

Therapeutic targeting of the TGF beta pathway

The TGF beta signaling pathway is a major therapeutic target:

  • Development of TGF-β neutralizing antibodies and receptor inhibitors
  • Targeting SMAD signaling and pathway cross-talk
  • Combination therapies with immune checkpoint inhibitors
  • Anti-fibrotic strategies to limit ECM deposition

Accurate biomarker profiling is essential to stratify patients and monitor therapeutic response.

Why study the TGF beta signaling pathway with AnyGenes®?

At AnyGenes®, we provide high-performance qPCR arrays and customizable SignArrays® dedicated to TGF-β pathway analysis.

Our solutions enable researchers to:

  • Quantify TGF-β-dependent gene expression signatures
  • Analyze SMAD-dependent and non-canonical signaling targets
  • Study EMT, fibrosis, and immune modulation markers
  • Generate robust, reproducible, publication-ready data

TGF beta signaling pathway biomarker analysis with AnyGenes®

What can be analyzed?

  • TGF-β ligands and receptors (TGF-β1-3, TGFBR1/2)
  • SMAD transcription factors and regulators
  • EMT and fibrosis-related genes
  • Immune suppression and tumor progression markers

Customize your own signaling pathways (SignArrays®) with the factors of your choice!
Simply download and complete our Personalized SignArrays® information file and send it at [email protected] to get started on your project.

Frequently asked questions

It is a multifunctional signaling pathway that regulates cell growth, differentiation, immune responses, and tissue remodeling through TGF-β receptor activation.

TGF-β suppresses early tumor growth but later promotes invasion, metastasis, immune evasion, and therapy resistance.

Persistent TGF-β activation stimulates extracellular matrix production, leading to tissue scarring and organ dysfunction.

By measuring expression of pathway regulators and downstream targets using targeted gene expression approaches such as qPCR pathway arrays.

  1. Suriyamurthy S et al. Epigenetic Reprogramming of TGF-β Signaling in Breast Cancer. Cancers (Basel). (2019) 24;11(5).
  2. Chen J et al. Immunomodulatory TGF-β Signaling in Hepatocellular Carcinoma. Trends Mol Med. (2019).
  3. Chen Y et al. Transforming growth factor β signaling pathway: A promising therapeutic target for cancer. J Cell Physiol. (2019).
  4. Batlle E et Massagué J. Transforming Growth Factor-β Signaling in Immunity and Cancer. Immunity. (2019) 16;50(4):924-940.
  5. Pellatt AJ et al.The TGFβ-signaling pathway and colorectal cancer: associations between dysregulated genes and miRNAs. J Transl Med. (2018);16(1):191.
  6. Papoutsoglou P et al. Transforming Growth Factor-Beta (TGFβ) Signaling Pathway in Cholangiocarcinoma.Cells. (2019)23;8(9).
  7. Neuzillet C et al. Targeting the TGFβ pathway for cancer therapy. PharmacolTher. (2015);147:22-31.
  8. Bellomo C et al. Transforming growth factor β as regulator of cancer stemness and metastasis. Br J Cancer. 2016 Sep 27;115(7):761-9.

TGF beta signaling pathway biomarker list

You can check the biomarker list included in this pathway, see below:

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