Hedgehog signalling pathway for breast cancer identified.


Molecules called long non-coding RNAs (lncRNAs) have been implicated in breast cancer but exactly why they cause metastasis and tumour growth has been little understood, until now.

Scientists at The MD Anderson Cancer Center report that hedgehog, a unique cell signalling pathway known to contribute to many types of cancer, may be behind breast cancer metastasis. This molecular message service works with the lncRNA known as BCAR4 giving the genetic green light for tumour growth.

The study of BCAR4 and the hedgehog signalling pathway has provided evidence for lncRNAs’ regulator roles in aggressive breast cancers progression.  Emerging evidence has revealed lncRNAs as a new class of players in the development and progression of cancer.

When the hedgehog signalling pathway is activated abnormally by proteins known as chemokines, it allows increased expression of genes controlled by a transcription factor called GLI2. Transcription factors are proteins that activate other genes. The team found that BCAR4 is required for GLI2-controlled gene activation. This molecular liaison of BCAR4 via the hedgehog signalling pathway and GLI2 is the first understanding of the tie between hedgehog and BCAR4 in breast cancer.

This new information led the researchers to explore the potential for an emerging therapy known as locked nucleic acids (LNA) for breast cancer.  Therapeutic targeting of lncRNAs has not been well documented for breast cancer. The current study aimed to determine their potential through use of an LNA-based therapy.

The group found that there was indeed a good outcome for LNAs in treating breast tumour spread when studied in mice, and human tissue and cell lines.

Therapeutic delivery of LNAs targeting BCAR4 strongly suppresses breast cancer metastasis. The team confirmed the link between BCAR4 and the hedgehog signalling pathway as a viable avenue for a new approach to treating aggressive breast cancers.

Source:  The University of Texas MD Anderson Cancer Center

 

Hedgehog signaling is a conserved developmental pathway involved in tissue and organ morphogenesis. The pathway was originally discovered in Drosophila melanogaster, and mammalian homologs were identified later. The 3 mammalian ligands (Sonic hedgehog, Desert hedgehog, and Indian hedgehog) bind to Patched receptor family members. Under basal conditions, Patched receptors repress Smoothened. When Hedgehog ligands bind to Patched, Smoothened is no longer inhibited, and enters the nucleus. Within the nucleus, Smoothened interacts and activates the Gli transcription factors by a poorly understood mechanism, activating target gene transcription. Hedgehog signaling is important during embryonic development. For example, the diffusion patterns of hedgehog ligands released into the extracellular matrix determine the location and orientation of limb development. Hedgehog signaling also remains important after development for adult stem cell proliferation and the maintenance and regeneration of organs. Dysregulation of hedgehog signaling is a cause of developmental abnormalities and some cancers. As the Hedgehog signaling mechanisms are fully elucidated, they may identify novel drug targets for these diseases.  © QIAGEN 2013–14. All rights reserved.

Hedgehog signaling is a conserved developmental pathway involved in tissue and organ morphogenesis. The pathway was originally discovered in Drosophila melanogaster, and mammalian homologs were identified later. The 3 mammalian ligands (Sonic hedgehog, Desert hedgehog, and Indian hedgehog) bind to Patched receptor family members. Under basal conditions, Patched receptors repress Smoothened. When Hedgehog ligands bind to Patched, Smoothened is no longer inhibited, and enters the nucleus. Within the nucleus, Smoothened interacts and activates the Gli transcription factors by a poorly understood mechanism, activating target gene transcription. Hedgehog signaling is important during embryonic development. For example, the diffusion patterns of hedgehog ligands released into the extracellular matrix determine the location and orientation of limb development. Hedgehog signaling also remains important after development for adult stem cell proliferation and the maintenance and regeneration of organs. Dysregulation of hedgehog signaling is a cause of developmental abnormalities and some cancers. As the Hedgehog signaling mechanisms are fully elucidated, they may identify novel drug targets for these diseases. © QIAGEN 2013–14. All rights reserved.

 

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Google photo

You are commenting using your Google account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s

This site uses Akismet to reduce spam. Learn how your comment data is processed.