SIP1, a target to prevent metastasis and a marker for breast cancer aggressiveness

Sip1 is a bio-marker for breast cancer stem cells, which are the cells responsible for tumor extension and metastasis. Sip1 can also be used therapeutically to inactivate breast cancer stem cells and as such treat breast cancer morbidity and mortality.

Summary of the Invention

IP1 (Smad-interaction protein 1), a multi-zinc finger transcriptional repressor, has been demonstrated to downregulate E-cadherin expression. This loss of E-cadherin results in reduced aggregation and acquisition of invasive properties and plays an important role in epithelial-to-mesenchymal transition (EMT) in cancers.

VIB scientists found that knocking down SIP1 expression in breast cancer cells resulted in

  • reduced mesenchymal morphology,
  • very reduced ability to migrate and
  • much stronger adhesion.

Furthermore, when injected in mammary fat pads of mice, tumor cells with knocked down SIP1 expression resulted halting tumor growth compared to the fast growing tumors of mice injected with control breast cancer stem cells. When injected in the tail vein of mice, cancer cells with knocked down SIP1 expression could home to and colonise the lungs in only 20 % of the mice, compared to 70 % with mice injected with control cancer cells. In xenographed human tumors and in human breast cancers the expression of SIP1 is limited to cancer stem cells, indicating its selectiveness.

Application

  • Biomarker for breast cancer stem cells which can be used for tumor classification
  • Therapeutic target¬†in breast cancer stem cells, which are at the basis of morbidity and mortality in breast cancer, amenable to antibody, peptide or RNAi inhibition
 
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