Highlights of This Issue

Abstract

Cancer-associated fibroblasts (CAF) secrete factors contributing to tumor angiogenesis, epithelial-to-mesenchymal transition (EMT), and cell motility as well as supporting the cancer stem cell (CSC) niche. Geary and colleagues identify annexin A1 (ANXA1) as a factor secreted by CAFs in the conditional Pten deletion mouse model of prostate adenocarcinoma, which induces EMT and stem cell characteristics to prostate epithelial tumor cells. Mechanistically, AnxA1 activates Mapk1 expression, leading to increases in TGFβ1 protein, as well as Snail, Twist, and Oct4 expression. In vivo, AnxA1 exposure facilitates terminally differentiated fractions of prostate adenocarcinoma cells to form complex glandular structures with increased expression of basal/progenitor cell marker p63 and higher pERK1/2 expression. This study provides new clues for an old molecule AnxA1 in the origin of prostate CSCs, and potentially CSCs in general.Resolving the complex role of autophagy in human cancer will be greatly aided by determining if essential autophagy genes are mutated or not. Beclin1, encoded by the essential autophagy gene BECN1, has been proposed to be a tumor suppressor, suggesting that autophagy suppresses tumorigenesis. In this Rapid Impact article, Laddha and colleagues report on their determination of the mutational status of BECN1 in 10,000 matched normal and human cancer specimens representing more than 30 distinct tumor types in The Cancer Genome Atlas and other databases. While mutations and deletions were found in other tumor suppressors, no recurrent mutations specifically in BECN1 were found in any cancer, suggesting that it is not a tumor suppressor.Kinesins are a large family of microtubule motor proteins that have been attractive targets for cancer therapeutics, largely due to their frequent deregulation. However, little is known about their deregulation mechanism. To this end, systematic molecular profiling of kinesin family expression in tamoxifen-sensitive and tamoxifen-resistant breast cancer cells exposed over 20 kinesins that are coordinately regulated by estrogen via the bromodomain protein ANCCA (ATAD2) and histone methyltransferase MLL1. Meta-analysis of tumor datasets indicated a strong prognostic association between members of the kinesins and ANCCA. These findings will be valuable for more effective cancer treatment with kinesin inhibitors and point to ANCCA as a new target.The increasing availability of genome-wide data on human cancers and cell lines provides an unprecedented opportunity to accurately and rationally select models for preclinical evaluation. Here, molecular analysis of head and neck carcinoma (HNC) specimens revealed genetic alterations that are restricted to human tumors or cell lines as well as mutations that are detected in both a subset of human cancers and cell model systems. Validation of pharmacologic profiling suggests that PIK3CA mutations serve as biomarkers of treatment resistance to targeted EGFR pathway inhibition. These findings underscore the critical importance of cell model selection in the context of clinical translation.