Related Experiment Video
Updated: Aug 6, 2026

The Soft Agar Colony Formation Assay
Published on: October 27, 2014
Suppression of cell proliferation and signaling transduction by connective tissue growth factor in non-small cell
Wenwen Chien1, Dong Yin, Dorina Gui
1Division of Hematology/Oncology, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, D5022, Los Angeles, CA 90048, USA.
Abstract:
Connective tissue growth factor (CTGF) is a secreted protein that belongs to CCN family. The proteins in this family are implicated in various biological processes, such as angiogenesis, adhesion, migration, and apoptosis. In this study, we explored the roles of CTGF in lung tumorigenesis. The expression levels of CTGF in 58 lung cancer samples were reduced by >2 fold in 57% of the samples compared with matched normal samples using real-time reverse transcription-PCR. These results were confirmed by immunohistochemical staining for CTGF in normal lung epithelia and lung cancer. Cellular proliferation was inhibited in non-small cell lung cancer (NSCLC) cell lines NCI-H460, NCI-H520, NCI-H1299, and SK-MES-1 by CTGF overexpression. Partially purified CTGF suppressed lung cancer cell growth. The growth inhibition caused by CTGF overexpression was associated with growth arrest at G(0)-G(1) and prominent induction of p53 and ADP ribosylation factor. Most interestingly, overexpression of CTGF suppressed insulin-like growth factor-I-dependent Akt phosphorylation and epidermal growth factor-dependent extracellular signal-regulated kinase 1/2 phosphorylation. In summary, NSCLC cells expressed decreased levels of CTGF compared with normal lung cells; this lower expression has an effect on lung cancer cell proliferation and its cellular response to growth factors. Our data suggest that CTGF may behave as a secreted tumor suppressor protein in the normal lung, and its expression is suppressed in many NSCLCs.
Insights
Connective tissue growth factor (CTGF) is often reduced in non-small cell lung cancer (NSCLC). Lower CTGF levels promote lung cancer cell proliferation, suggesting CTGF acts as a tumor suppressor.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Connective tissue growth factor (CTGF) is a CCN family member involved in cell adhesion, migration, and apoptosis.
- Understanding CTGF's role in lung tumorigenesis is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the expression and function of CTGF in non-small cell lung cancer (NSCLC).
- To determine if CTGF acts as a tumor suppressor in lung cancer development.
Main Methods:
- Real-time reverse transcription-PCR and immunohistochemical staining to assess CTGF expression in lung cancer samples and cell lines.
- Overexpression of CTGF in NSCLC cell lines to evaluate its effects on cellular proliferation and cell cycle.
- Analysis of downstream signaling pathways, including Akt and ERK phosphorylation, in response to CTGF modulation.
Main Results:
- CTGF expression was significantly reduced in 57% of 58 NSCLC samples compared to normal lung tissue.
- CTGF overexpression inhibited proliferation and induced G(0)-G(1) growth arrest in NSCLC cell lines.
- CTGF overexpression suppressed insulin-like growth factor-I-dependent Akt and epidermal growth factor-dependent ERK phosphorylation.
Conclusions:
- Decreased CTGF expression is a common feature in NSCLC and correlates with increased tumor cell proliferation.
- CTGF may function as a secreted tumor suppressor protein in the lung, with its suppression contributing to lung cancer progression.
Related Concept Videos
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
Mitogens and the Cell Cycle
Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
TGF - β Signaling Pathway
Regulation of Angiogenesis and Blood Supply
Abnormal Proliferation