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TGF-β1-mediated intercellular signaling fuels cooperative cellular invasion
Tala O Khatib1, Brian A Pedro2, Sergei Bombin3
1Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA; Winship Cancer Institute of Emory University, Atlanta, GA 30322, USA; Graduate Program in Biochemistry, Cell, and Developmental Biology, Emory University, Atlanta, GA 30322, USA.
Cell Reports
|February 16, 2025
Summary
Cancer cells communicate to drive tumor growth and spread. This study shows how non-small cell lung cancer subpopulations cooperate through transforming growth factor beta one (TGF-β1) signaling, impacting invasion and metastasis.
Area of Science:
- Oncology
- Cell Biology
- Cancer Research
Background:
- Intratumoral heterogeneity is a key driver of cancer progression and treatment resistance.
- Mechanisms of cellular subpopulation communication in cancer remain poorly understood.
Purpose of the Study:
- To deconstruct the cooperative mechanisms of non-small cell lung cancer (NSCLC) subpopulations during collective invasion.
- To elucidate the role of intercellular communication in maintaining tumor heterogeneity and promoting progression.
Main Methods:
- Utilized collective invasion as a model system for NSCLC.
- Analyzed heterogeneously cycling and non-cycling subpopulations within invading packs.
- Investigated the role of transforming growth factor beta one (TGF-β1) and JAG1 signaling.
Main Results:
- Collectively invading NSCLC packs comprise distinct cycling and non-cycling subpopulations.
- Follower subpopulations secrete TGF-β1, inducing context-dependent responses in leader subpopulations.
- TGF-β1 promotes proliferation in isolated followers but quiescence in isolated leaders; however, leaders in heterogeneous populations proliferate to maintain proportions.
- JAG1-dependent invasion is stimulated by TGF-β1.
- Both leader and follower subpopulations are essential for metastatic progression in vivo.
Conclusions:
- Intercellular communication, particularly TGF-β1 signaling, is crucial for preserving tumor cell heterogeneity.
- This communication facilitates collective behaviors like invasion and progression in NSCLC.
- Targeting these communication pathways may offer therapeutic strategies against metastatic cancer.
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