Nat Commun: Smad4 deletion inhibits PAK3 expression and promotes metastasis of invasive lung cancer

Lung cancer is the leading cause of cancer-related deaths worldwide and can be roughly divided into small cell lung cancer and non-small cell lung cancer ( NSCLC )
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More than 85% of lung cancers are classified as NSCLC

Lung cancer is the leading cause of cancer-related deaths worldwide and can be roughly divided into small cell lung cancer and non-small cell lung cancer ( NSCLC )

As a tumor suppressor, Smad4 is the central intracellular mediator of the TGF-β signal transduction pathway
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Studies have shown that the inactivation of Smad4 is related to different types of cancer

As a tumor suppressor, Smad4 is the central intracellular mediator of the TGF-β signal transduction pathway

In this study, the researchers constructed a highly aggressive lung cancer mouse model with conditional Kras G12D mutation, p53fl/fl LOF mutation and Smad4fl/fl LOF mutation (SPK).
fl(PK) mice have a higher incidence of tumor metastasis
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Smad4 deletion will accelerate the occurrence and metastasis of lung cancer

Smad4 deletion will accelerate the occurrence and metastasis of lung cancer

The researchers found that PAK3 is a downstream effector of Smad4, which can mediate the transduction of metastatic signals through the PAK3-JNK-Jun signaling pathway
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The up-regulation of PAK3 expression by Smad4 LOF in SPK mice was achieved by attenuating the Smad4-dependent transcription of microRNA miR-495 and miR-543

PAK3 is a downstream effector of Smad4, which can mediate the transduction of metastatic signals through the PAK3-JNK-Jun signaling pathway

Smad4 deficiency promotes the migration and invasion of lung cancer cells

Smad4 deficiency promotes the migration and invasion of lung cancer cells

These miRNAs can directly bind to the 3'UTR region of PAK3 and block the production of PAK3, ultimately regulating the metastasis of lung cancer
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Further studies have also observed a negative correlation between Smad4 and PAK3 pathway components in human lung cancer

All in all, the results of this study emphasize that Smad4-PAK3 regulation is a potential therapeutic target for metastatic lung cancer
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The results of this study emphasize that Smad4-PAK3 regulation is a potential therapeutic target for metastatic lung cancer
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The results of this study emphasize that Smad4-PAK3 regulation is a potential therapeutic target for metastatic lung cancer

Loss of Smad4 promotes aggressive lung cancer metastasis by de-repression of PAK3 via miRNA regulation

 

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