Teneurins: Role in Cancer and Potential Role as Diagnostic Biomarkers and Targets for Therapy

Teneurins have been identified in vertebrates as four different genes (TENM1-4), coding for membrane proteins that are mainly involved in embryonic and neuronal development. Genetic studies have correlated them with various diseases, including developmental problems, neurological disorders and congenital general anosmia. There is some evidence to suggest their possible involvement in cancer initiation and progression, and drug resistance. Indeed, mutations, chromosomal alterations and the deregulation of teneurins expression have been associated with several tumor types and patient survival. However, the role of teneurins in cancer-related regulatory networks is not fully understood, as both a tumor-suppressor role and pro-tumoral functions have been proposed, depending on tumor histotype. Here, we summarize and discuss the literature data on teneurins expression and their potential role in different tumor types, while highlighting the possibility of using teneurins as novel molecular diagnostic and prognostic biomarkers and as targets for cancer treatments, such as immunotherapy, in some tumors

Immunotargeting of antigen xCT attenuates stem-like cell behavior and metastatic progression in breast cancer

Abstract Resistance to therapy and lack of curative treatments for metastatic breast cancer suggest that current therapies may be missing the subpopulation of chemoresistant and radioresistant cancer stem cells (CSC). The ultimate success of any treatment may well rest on CSC eradication, but specific anti-CSC therapies are still limited. A comparison of the transcriptional profiles of murine Her2+ breast tumor TUBO cells and their derived CSC-enriched tumorspheres has identified xCT, the functional subunit of the cystine/glutamate antiporter system xc−, as a surface protein that is upregulated specifically in tumorspheres. We validated this finding by cytofluorimetric analysis and immunofluorescence in TUBO-derived tumorspheres and in a panel of mouse and human triple negative breast cancer cell-derived tumorspheres. We further show that downregulation of xCT impaired tumorsphere generation and altered CSC intracellular redox balance in vitro, suggesting that xCT plays a functional role in CSC biology. DNA vaccination based immunotargeting of xCT in mice challenged with syngeneic tumorsphere-derived cells delayed established subcutaneous tumor growth and strongly impaired pulmonary metastasis formation by generating anti-xCT antibodies able to alter CSC self-renewal and redox balance. Finally, anti-xCT vaccination increased CSC chemosensitivity to doxorubicin in vivo, indicating that xCT immunotargeting may be an effective adjuvant to chemotherapy. Cancer Res; 76(1); 62–72. ©2015 AACR.</jats:p

Employing a spatio-temporal contingency table for the analysis of cork oak cover change in the Sa Serra region of Sardinia

Land cover change analyses are common and, especially in the absence of explanatory variables, they are mainly carried out by employing qualitative methods such as transition matrices or raster operations. These methods do not provide any estimation of the statistical significance of the changes, or the uncertainty of the model and data, and are usually limited in supporting explicit biological/ecological interpretation of the processes determining the changes. Here we show how the original nearest-neighbour contingency table, proposed by Dixon to evaluate spatial segregation, has been extended to the temporal domain to map the intensity, statistical significance and uncertainty of land cover changes. This index was then employed to quantify the changes in cork oak forest cover between 1998 and 2016 in the Sa Serra region of Sardinia (Italy). The method showed that most statistically significant cork oak losses were concentrated in the centre of Sa Serra and characterised by high intensity. A spatial binomial-logit generalised linear model estimated the probability of changes occurring in the area but not the type of change. We show how the spatio-temporal Dixon’s index can be an attractive alternative to other land cover change analysis methods, since it provides a robust statistical framework and facilitates direct biological/ecological interpretation