Related Experiment Videos

Matrix protein CCN1 is critical for prostate carcinoma cell proliferation and TRAIL-induced apoptosis

Carrie A Franzen1, Chih-Chiun Chen, Viktor Todorović

  • 1Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago College of Medicine, Chicago, IL 60607, USA.

Molecular Cancer Research : MCR
|July 9, 2009
PubMed

Insights

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) enhances prostate cancer cell death. CCN1 protein promotes cancer growth but also sensitizes cells to TRAIL therapy, suggesting its expression impacts treatment efficacy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) shows promise for cancer therapy due to selective cancer cell apoptosis induction.
  • The molecular mechanisms underlying TRAIL's selective action remain unclear.
  • CCN family proteins are matricellular regulators of cell behavior.

Purpose of the Study:

  • To investigate the role of CCN1 (CYR61) in prostate carcinoma cell adhesion, proliferation, and sensitivity to TRAIL-induced apoptosis.
  • To elucidate the molecular interactions and pathways involved in CCN1's function.

Main Methods:

  • Knockdown of CCN1 expression in prostate cancer cell lines (PC-3, DU-145, LNCaP).
  • Assessment of cell proliferation and apoptosis.
  • Analysis of CCN1 interaction with integrins (alphavbeta3, alpha6beta4) and syndecan-4.
  • Investigation of protein kinase Calpha involvement.
  • Reversal of effects using exogenous CCN1 protein.

Main Results:

  • CCN1 promotes the adhesion and proliferation of prostate carcinoma cells.
  • CCN1 enhances TRAIL-induced apoptosis through integrin and syndecan-4 interactions via a PKCalpha-dependent pathway.
  • CCN1 knockdown significantly reduces sensitivity to TRAIL-induced apoptosis, an effect reversible by adding CCN1 protein.

Conclusions:

  • CCN1 exhibits a dual role in prostate carcinoma, promoting proliferation and enhancing TRAIL-induced cell death.
  • CCN1 expression levels may serve as a predictive biomarker for TRAIL-based cancer therapy efficacy.

Related Concept Videos

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...
Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which results in tumor...
Positive Regulator Molecules02:39

Positive Regulator Molecules

Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
Cancer-Critical Genes I: Proto-oncogenes01:33

Cancer-Critical Genes I: Proto-oncogenes

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...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
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 daughter...