Involvement of integrin-activating peptides derived from tenascin-C in colon cancer progression

Tenascin-C(TNC)is an adhesion modulatory protein present in the extracellular matrix that is highly expressed in several malignancies,including colon cancer.Although TNC is considered a negative prognostic factor for cancer patients,the substantial role of the TNC molecule in colorectal carcinogenesis and its malignant progression is poorly understood.We previously found that TNC has a cryptic functional site and that a TNC peptide containing this site,termed TNIIIA2,can potently and persistently activate beta1-integrins.In contrast,the peptide FNIII14,which contains a cryptic bioactive site within the fibronectin molecule,can inactivate beta1-integrins.This review presents the role of TNC in the development of colitis-associated colorectal cancer and in the malignant progression of colon cancer,particularly the major involvement of its cryptic functional site TNIIIA2.We propose new possible prophylactic and therapeutic strategies based on inhibition of the TNIIIA2-induced beta1-integrin activation by peptide FNIII14.

Inhibition of growth and metastasis of triple-negative breast cancer targeted by Traditional Chinese Medicine Tubeimu in orthotopic mice models

Objective： Triple-negative breast cancer（TNBC） is highly invasive and metastatic, which is in urgent need of transformative therapeutics. Tubeimu（TBM）, the rhizome of Bolbostemma paniculatum（Maxim.） Franquet, is one of the Chinese medicinal herbs used for breast diseases since the ancient times. The present study evaluated the efficacy, especially the anti-metastatic effects of the dichloromethane extract of Tubeimu（ETBM） on TNBC orthotopic mouse models and cell lines.Methods： We applied real-time imaging on florescent orthotopic TNBC mice model and tested cell migration and invasion abilities with MDA-MB-231 cell line. Digital gene expression sequencing was performed and Kyoto Encyclopedia of Genes and Genomes（KEGG） analysis applied to explore the pathways influenced by ETBM.Moreover, quantitative real-time polymerase chain reactions（q RT-PCR） and Western blot were delivered to confirm the gene expression changes.Results： ETBM exhibited noticeable control on tumor metastasis and growth of TNBC tumors with no obvious toxicity. In compliance with this, it also showed inhibition of cell migration and invasion in vitro. Its impact on the changed biological behavior in TNBC may be a result of decreased expression of integrin β1（ITGβ1）, integrin β8（ITGβ8） and Rho GTPase activating protein 5（ARHGAP5）, which disabled the focal adhesion pathway and caused change in cell morphology.Conclusions： This study reveals that ETBM has anti-metastatic effects on MDA-MB-231-GFP tumor and may lead to a new therapeutic agent for the integrative treatment of highly invasive TNBC.