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New biomarker highly promising for predicting breast cancer outcomes.

A protein named p66ShcA shows promise as a biomarker to identify breast cancers with poor prognoses, according to research published in the journal Molecular and Cellular Biology.

Cancer is deadly in large part due to its ability to metastasize, to travel from one organ or tissue type to another and malignantly sprout anew. The vast majority of cancer deaths are associated with metastasis.

In breast cancer, a process called ‘epithelial to mesenchymal transition’ aids metastasis. Epithelial cells line surfaces which come into contact with the environment, such as skin and the gastrointestinal tract. Mesenchymal cells are a type of cell in embryonic tissue and in connective tissue, where they form very loose contacts with one-another. Tumour cells lose mature epithelial characteristics, such as the ability to adhere to their neighbours, and gain those of the mesenchymal cells which enable them to move easily through the cellular matrix and into the blood stream. That enables their metastatic migration to distant organs and tissues.

The researchers, led by McGill University, show that the protein p66ShcA is highly enriched in breast cancers that have undergone epithelial to mesenchymal transition.

The team showed that elevated p66ShcA expression levels are strongly associated with expression of numerous epithelial to mesenchymal transition genes in all breast cancer subtypes.  Thus, p66ShcA may serve as one of the first prognostic biomarkers to identify poor outcome breasts cancers regardless of their molecular subtype.

The ability to predict prognosis is critical to management of treatment. A patient with a good prognosis can be spared aggressive treatment, with its oft-unpleasant side effects. But failure to apply aggressive treatment to an aggressive tumour can lead to death.

Breast cancers stratify into at least five subtypes, each of which is associated with a different outcome. Nonetheless, earlier research showed that there is heterogeneity within the subtypes, which makes predictions of outcome based on subtype less reliable than they might otherwise be.

By understanding the underlying mechanisms that contribute to tumour heterogeneity and metastatic progression, including the epithelial to mesenchymal transition, the group hope to be better able to guide the development of prognostic and therapeutic strategies to improve patient care.

Source:  McGill University  

Proposed model for the role of p66ShcA in promoting plasticity among the various breast cancer subtypes.  Within the luminal subtype, breast tumours uniformly express Cytokeratin 8/18, along with adherens (E-Cadherin) and tight junctional (ZO1, Claudins) proteins.  However, a subset of these tumours also express EMT-like genes (Vimentin, N-Cadherin, Snai1/2, Zeb 1/2, Twist1/2) without the obligate loss of E-Cadherin expression. We propose that elevated p66ShcA expression in luminal breast cancer cells endows them with such a partial EMT phenotype to increase their plasticity leading to enhanced cell migration and invasion. In contrast, within the basal subtype.  Basal-like tumours co-express luminal (CK8/18) and myoepithelial (CK14, SMA) markers while claudin-low tumours uniformly lack luminal epithelial markers and stably express mesenchymal genes indicative of a complete EMT. We propose that elevated p66ShcA overexpression in the basal subtype further drives an EMT to promote the development of claudin low breast tumours.  Ursini-Siegel et al 2014.
Proposed model for the role of p66ShcA in promoting plasticity among the various breast cancer subtypes. Within the luminal subtype, breast tumours uniformly express Cytokeratin 8/18, along with adherens (E-Cadherin) and tight junctional (ZO1, Claudins) proteins. However, a subset of these tumours also express EMT-like genes (Vimentin, N-Cadherin, Snai1/2, Zeb 1/2, Twist1/2) without the obligate loss of E-Cadherin expression. We propose that elevated p66ShcA expression in luminal breast cancer cells endows them with such a partial EMT phenotype to increase their plasticity leading to enhanced cell migration and invasion. In contrast, within the basal subtype. Basal-like tumours co-express luminal (CK8/18) and myoepithelial (CK14, SMA) markers while claudin-low tumours uniformly lack luminal epithelial markers and stably express mesenchymal genes indicative of a complete EMT. We propose that elevated p66ShcA overexpression in the basal subtype further drives an EMT to promote the development of claudin low breast tumours. Ursini-Siegel et al 2014.

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Michelle Petersen is the founder of Healthinnovations, having worked in the health and science industry for over 21 years, which includes tenure within the NHS and Oxford University. Healthinnovations is a publication that has reported on, influenced, and researched current and future innovations in health for the past decade.

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Most recently the Texas A&M University covered The Top 10 Healthinnovations series on their site with distinguished Professor Stephen Maren calling the inclusion of himself and his team on the list a reflection of “the hard work and dedication of my students and trainees”.

Michelle Petersen’s copy was used in the highly successful marketing campaign for the mega-hit film ‘Jumanji: The Next Level, starring Jack Black, Karen Gilian, Kevin Hart and Dwayne ‘The Rock’ Johnson. Michelle Petersen’s copywriting was part of the film’s coverage by the Republic TV network. Republic TV is the most-watched English language TV channel in India since its inception in 2017.

An avid campaigner in the fight against child sex abuse and trafficking, Michelle is a passionate humanist striving for a better quality of life for all humans by helping to provide traction for new technologies and techniques within healthcare.

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