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Transforming Growth Factor-Beta (TGF-β) Signaling in Cancer-A Betrayal Within

Abdul Basit Baba¹, Bilal Rah¹, Gh Rasool Bhat¹

¹Advanced Centre for Human Genetics, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, India.

Frontiers in Pharmacology

|March 17, 2022

Abstract:

A ubiquitously expressed cytokine, transforming growth factor-beta (TGF-β) plays a significant role in various ongoing cellular mechanisms. The gain or loss-of-function of TGF-β and its downstream mediators could lead to a plethora of diseases includes tumorigenesis. Specifically, at the early onset of malignancy TGF-β act as tumour suppressor and plays a key role in clearing malignant cells by reducing the cellular proliferation and differentiation thus triggers the process of apoptosis. Subsequently, TGF-β at an advanced stage of malignancy promotes tumorigenesis by augmenting cellular transformation, epithelial-mesenchymal-transition invasion, and metastasis. Besides playing the dual roles, depending upon the stage of malignancy, TGF-β also regulates cell fate through immune and stroma components. This oscillatory role of TGF-β to fight against cancer or act as a traitor to collaborate and crosstalk with other tumorigenic signaling pathways and its betrayal within the cell depends upon the cellular context. Therefore, the current review highlights and understands the dual role of TGF-β under different cellular conditions and its crosstalk with other signaling pathways in modulating cell fate.

Insights

Transforming growth factor-beta (TGF-β) has a dual role in cancer, acting as a tumor suppressor early on and a promoter in later stages. Its function depends on cellular context and interactions with other signaling pathways.

Area of Science:

Cellular Biology
Molecular Oncology
Immunology

Background:

Transforming growth factor-beta (TGF-β) is a cytokine involved in numerous cellular processes.
Dysregulation of TGF-β signaling contributes to various diseases, including cancer.
TGF-β exhibits context-dependent roles in malignancy, acting as both a tumor suppressor and promoter.

Purpose of the Study:

To review the dual role of TGF-β in cancer progression.
To understand the mechanisms underlying TGF-β's context-dependent functions.
To explore TGF-β's crosstalk with other signaling pathways in cancer.

Main Methods:

Literature review of studies on TGF-β in cancer.
Analysis of TGF-β's roles at different malignancy stages.
Examination of TGF-β's interactions with cellular and molecular components.

Main Results:

Early-stage cancer: TGF-β suppresses tumors by inhibiting proliferation, promoting differentiation, and inducing apoptosis.
Advanced-stage cancer: TGF-β promotes tumorigenesis via enhanced cellular transformation, epithelial-mesenchymal transition, invasion, and metastasis.
TGF-β influences cell fate by modulating immune and stromal components.

Conclusions:

TGF-β's role in cancer is complex and depends on the cellular context and stage of malignancy.
TGF-β signaling can be hijacked by cancer cells to promote tumor growth and spread.
Understanding TGF-β's dual functions and crosstalk is crucial for developing effective cancer therapies.

Read full analysis

Keywords:

TGF-β 1 metastasis signaling pathways tumor suppressor tumorigenesis

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