Researchers Identify New Lung Cancer Suppressor Gene

Researchers Identify New Lung Cancer Suppressor Gene

shutterstock_133446737A Spanish research team has identified the PARD3 gene as a lung cancer suppressor. The study entitled “PARD3 Inactivation in Lung Squamous Cell Carcinomas Impairs STAT3 and Promotes Malignant Invasion” was published in the journal Cancer Research.

Lung cancer is the third most common cancer in the US after prostate and breast cancers, according to the National Cancer Institute. This type of cancer has a very high mortality rate, with a 10-15% survival rate 5 years after diagnosis.

About 85% of all lung cancers are non-small cell lung cancer (NSCLC), which can be subdivided into lung adenocarcinomas (LAC) and lung squamous cell carcinomas (LSCC) based on tissue architecture, cell morphology and gene alterations. LSCC accounts for about 30% of all NSCLC and is strongly associated with smoking. Alterations to gene expression profiles in this type of cancer are still not well established when compared to LAC.

In this recent study, researchers investigated gene alterations associated with LSCC leading to gene inactivation of tumor suppressor genes in these lung cancer cells, observing the PARD3 gene was inactivated in 8% of LSCCs — a frequency of inactivation similar to other important suppressor genes.

The PARD3 gene codes for a protein involved in formation of intracellular adhesion areas — known as tight junctions — between epithelial cells. This protein also contributes to asymmetric organization of epithelial cells (cell polarity), important in separating different compartments. Importantly, the research team was able to show that expression of the PAR3 gene in LSCC prevented the development of metastasis in animal models, most likely by reestablishing intercellular recognition and increasing cell-to-cell interactions. In agreement with this study, the depletion of PAR3 in mice leads to increased metastasis.

“In conclusion, we report recurrent and tumor-specific inactivation of PARD3 in LSCC, which leaves little doubt that it acts as a bona fide tumor suppressor gene. Our findings also highlight how PARD3 inactivation contributes to LSCC development and metastasis through the abrogation of some important properties of epithelial cells, such as cell–cell recognition and the formation of cell contacts,” the authors explained.

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