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The Role of the Transforming Growth Factor-β Signaling Pathway in Gastrointestinal Cancers

Tasuku Matsuoka¹, Masakazu Yashiro¹

¹Molecular Oncology and Therapeutics, Osaka Metropolitan University Graduate School of Medicine, Osaka 5458585, Japan.

|October 28, 2023

Abstract:

Transforming growth factor-β (TGF-β) has attracted attention as a tumor suppressor because of its potent growth-suppressive effect on epithelial cells. Dysregulation of the TGF-β signaling pathway is considered to be one of the key factors in carcinogenesis, and genetic alterations affecting TGF-β signaling are extraordinarily common in cancers of the gastrointestinal system, such as hereditary nonpolyposis colon cancer and pancreatic cancer. Accumulating evidence suggests that TGF-β is produced from various types of cells in the tumor microenvironment and mediates extracellular matrix deposition, tumor angiogenesis, the formation of CAFs, and suppression of the anti-tumor immune reaction. It is also being considered as a factor that promotes the malignant transformation of cancer, particularly the invasion and metastasis of cancer cells, including epithelial-mesenchymal transition. Therefore, elucidating the role of TGF-β signaling in carcinogenesis, cancer invasion, and metastasis will provide novel basic insight for diagnosis and prognosis and the development of new molecularly targeted therapies for gastrointestinal cancers. In this review, we outline an overview of the complex mechanisms and functions of TGF-β signaling. Furthermore, we discuss the therapeutic potentials of targeting the TGF-β signaling pathway for gastrointestinal cancer treatment and discuss the remaining challenges and future perspectives on targeting this pathway.

Insights

Transforming growth factor-β (TGF-β) signaling is crucial in gastrointestinal cancers. Targeting TGF-β offers potential for new therapies against cancer invasion and metastasis.

Area of Science:

Oncology
Molecular Biology
Gastroenterology

Background:

Transforming growth factor-β (TGF-β) acts as a tumor suppressor in epithelial cells.
Dysregulation of TGF-β signaling is a key factor in carcinogenesis, particularly in gastrointestinal cancers.
Genetic alterations in TGF-β signaling are common in hereditary nonpolyposis colon cancer and pancreatic cancer.

Purpose of the Study:

To review the complex mechanisms and functions of TGF-β signaling in cancer.
To discuss the therapeutic potential of targeting TGF-β signaling in gastrointestinal cancers.
To explore challenges and future perspectives in TGF-β targeted therapy.

Main Methods:

Literature review of TGF-β signaling pathways.
Analysis of TGF-β's role in tumor microenvironment.
Evaluation of therapeutic strategies targeting TGF-β.

Main Results:

TGF-β mediates extracellular matrix deposition, angiogenesis, CAF formation, and immune suppression.
TGF-β promotes cancer malignant transformation, invasion, and metastasis, including epithelial-mesenchymal transition.
Elucidating TGF-β signaling provides insights for diagnosis, prognosis, and targeted therapies.

Conclusions:

TGF-β signaling plays a dual role in cancer, acting as both a suppressor and promoter.
Targeting TGF-β signaling presents therapeutic opportunities for gastrointestinal cancers.
Further research is needed to overcome challenges and optimize TGF-β targeted therapies.

Read full analysis

Keywords:

epithelial-mesenchymal transition gastrointestinal cancers immune evasion smad targeted therapy transforming growth factor-β tumor microenvironment

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