Control of cancer stem cell like population by intracellular target identification followed by the treatment with peptide-siRNA complex

• Published in: Biochemical and biophysical research communications 2017-09, Vol.491 (3), p.827-833
• Main Authors: Suh, Jin Sook, Lee, Hyun Jung, Nam, Hyun, Jo, Beom Soo, Lee, Dong Woo, Kim, Ji-Hye, Lee, Jue Yeon, Chung, Chong Pyoung, Lee, Gene, Park, Yoon Jeong
• Format: Article
• Language: English
• Subjects: Apoptosis - drug effects; Apoptosis - genetics; Cell Line, Tumor; Cell penetrating peptide; Epithelial-to-mesenchymal transition; FER siRNA delivery; FER tyrosine kinase; Gene Silencing; Gene Targeting - methods; Genetic Therapy - methods; Human breast cancer stem cells; Humans; Molecular Targeted Therapy - methods; Neoplastic Stem Cells - drug effects; Neoplastic Stem Cells - physiology; Peptides - administration & dosage; Peptides - pharmacokinetics; Pluripotency; Protein-Tyrosine Kinases - antagonists & inhibitors; Protein-Tyrosine Kinases - genetics; RNA, Small Interfering - genetics; RNA, Small Interfering - therapeutic use; Treatment Outcome
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2017.05.148

Cancer stem cells (CSCs) are a subpopulation of cancer cells and have been known to create cancer reoccurrence during cancer therapy due to their stem cell-like characteristics. However, exact target to control the CSC has not been fully established. Here, we enriched CD44High population of MDA-MB-231 cells by CD44 antibody as a CSC marker. By Phospho Antibody Array, CD44High population of MDA-MB-231 cells reveals Feline sarcoma-related tyrosine kinase (FER) protein was highly activated. When FER siRNA and low molecular weight protamine (LMWP) as cell penetrating peptides are applied to this population, cancer migration and colony forming ability are inhibited. Moreover, silencing FER using FER siRNA and LMWP conjugates enhances anti-metastasis related factors including E-cadherin, p75 and p63. Taken together, FER is a new marker for targeting breast CSCs and peptide-mediated siRNA method could be an effective and safe way of delivery and be a new therapeutic strategy for targeting breast cancer. •FER protein is highly activated in the cancer stem cells derived from human breast tumors.•Silencing FER by siRNA reduces stemness and metastatic features of cancer stem cells.•FER siRNA complex with the cell-penetrating peptide showed more effective and less toxic method.