Biological functions and molecular interactions of Wnt/ß-catenin in breast cancer: Revisiting signaling networks.

Changes in lifestyle such as physical activity and eating habits have been one of the main reasons for development of various diseases in modern world, especially cancer. However, role of genetic factors in initiation of cancer cannot be ignored and Wnt/ß-catenin signaling is such factor that can affect tumor progression. Breast tumor is the most malignant tumor in females and it causes high mortality and morbidity around the world. The survival and prognosis of patients are not still desirable, although there have been advances in introducing new kinds of therapies and diagnosis. The present review provides an update of Wnt/ß-catenin function in breast cancer malignancy. The upregulation of Wnt is commonly observed during progression of breast tumor and confirms that tumor cells are dependent on this pathway Wnt/ß-catenin induction prevents apoptosis that is of importance for mediating drug resistance. Furthermore, Wnt/ß-catenin signaling induces DNA damage repair in ameliorating radio-resistance. Wnt/ß-catenin enhances proliferation and metastasis of breast tumor. Wnt/ß-catenin induces EMT and elevates MMP expression. Furthermore, Wnt/ß-catenin participates in tumor microenvironment remodeling and due to its tumor-promoting factor, drugs for its suppression have been developed. Different kinds of upstream mediators Wnt/ß-catenin signaling in breast cancer have been recognized that their targeting is a therapeutic approach. Finally, Wnt/ß-catenin can be considered as a biomarker in clinical trials.

Long non-coding RNA/epithelial-mesenchymal transition axis in human cancers: Tumorigenesis, chemoresistance, and radioresistance.

Epithelial-to-mesenchymal transition (EMT) is a process that involves the transformation of polarized epithelial cells to attain a mesenchymal phenotype that presents an elevated migratory potential, invasiveness, and antiapoptotic properties. Many studies have demonstrated that EMT is a prominent event that is associated with embryogenesis, tumor progression, metastasis, and therapeutic resistance. The EMT process is driven by key transcription factors (such as Snail, Twist, ZEB, and TGF-ß) and several long non-coding RNAs (lncRNAs) in many non-pathological as well as pathological conditions. In the present report, we have comprehensively discussed the oncogenic and tumor suppressor role of lncRNAs and their mechanism of action in the regulation of the EMT process in various cancers such as brain tumors, gastrointestinal tumors, and gynecological and urological tumors. We have also elaborated on the role of lncRNAs in the regulation of EMT-related transcription factors (such as Snail, Twist, ZEB, and TGF-ß) and therapeutic response (chemoresistance and radioresistance). Lastly, we have emphasized the role of exosomal lncRNAs in the regulation of EMT, metastasis, and therapeutic response in the aforementioned cancers. Taken together, this review provides a detailed insight into the understanding of role of lncRNAs/exosomal lncRNAs in EMT, metastasis, and therapeutic response in human cancers.