Expression and significance of transforming growth factor-β receptor type II and DPC4/Smad4 in non-small cell lung

Hong Chen1, Jing-Wei Wang2, Li-Xin Liu2

  • 1Department of Radiotherapy and Chemotherapy, Tangshan Gongren Hospital, Tangshan, Hebei 063000, P.R. China.

Insights

Transforming growth factor-β (TGF-β) receptor type II (TβRII) and DPC4/Smad4 expression are significantly lower in non-small cell lung cancer (NSCLC). Reduced levels correlate with poor differentiation and metastasis, indicating their role in NSCLC progression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related mortality.
  • The transforming growth factor-β (TGF-β) signaling pathway is crucial in cell growth and differentiation.
  • Dysregulation of TGF-β signaling is implicated in various cancers, including NSCLC.

Purpose of the Study:

  • To investigate the expression levels of TGF-β receptor type II (TβRII) and DPC4/Smad4 in NSCLC.
  • To determine the association between TβRII and DPC4/Smad4 expression and clinical-pathological features of NSCLC.
  • To elucidate the role of TβRII and DPC4/Smad4 in NSCLC tumorigenesis and progression via the TGF-β pathway.

Main Methods:

  • Quantitative analysis of TβRII and DPC4/Smad4 mRNA and protein expression using RT-qPCR and Western blotting.
  • Immunohistochemical detection of DPC4/Smad4 protein in NSCLC tissues.
  • Correlation analysis between gene/protein expression and clinical-pathological parameters in 60 NSCLC patients.

Main Results:

  • Significantly lower expression of TβRII and DPC4/Smad4 in NSCLC tissues compared to non-lesional lung tissues.
  • Reduced expression of TβRII and DPC4/Smad4 in poorly-differentiated NSCLC and tissues with lymph node metastasis.
  • Expression levels correlated significantly with clinical-pathological stages of NSCLC.

Conclusions:

  • TβRII and DPC4/Smad4 expression levels are significantly reduced in NSCLC.
  • These reduced levels are associated with tumor progression, differentiation, and metastasis.
  • TβRII and DPC4/Smad4 play a critical role in NSCLC development and progression through the TGF-β signaling pathway.

Related Concept Videos

TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
11.1K
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
8.5K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.5K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
5.1K
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
10.5K
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
4.0K