Highlights of This Issue Free

Long noncoding RNA (lncRNA) molecules are generally more than 200 bp in length and are currently the subject of intense research due to a number of commonalities with coding RNAs, such as association with polymerase II, polyadenylation, and transcriptionally linked epigenetic marks. Despite this intense focus, the translational relevance to cancer has only been described for a few lncRNAs. This Rapid Impact article by Malik and colleagues reveals that prostate cancer–associated transcript 29 (PCAT29) is regulated in a hormone-dependent manner. Importantly, PCAT29 is the first androgen-repressed lncRNA identified that has tumor-suppressor qualities, and reduced expression of PCAT29 predicts a higher risk of disease recurrence.

In considering therapeutic opportunities for poly (ADP-ribose) polymerase (PARP) inhibitors, knowledge of the DNA repair status of the target cancer is important. Thus, tumor cells that are deficient in double-strand break (DSB) DNA repair are sensitive to PARP inhibitors, and this is a basis for selecting monotherapy with these agents. Horton and colleagues demonstrate that deficiencies in major base excision repair (BER) proteins, such as pol β or XRCC1, render cells hypersensitive to PARP inhibition. This information is valuable for therapeutic consideration because it expands the types of DNA repair deficiencies that can be exploited for monotherapy with clinically relevant PARP inhibitors.

Different biologic functions have been attributed to the various spliced isoforms of the tyrosine protein kinase ERBB4, which may contribute to variable association of ERBB4 expression with carcinoma. Wali and colleagues produced isogenic lines that express ERBB4 isoforms in basal-like and luminal-like mammary carcinoma cells. Subsequent study revealed the importance of ERBB4 in the transcriptional regulation of Hippo and mevalonate pathway targets. Candidate coregulatory targets for ERBB4 were identified by ChIP-Seq. These findings clarify the diverse activities of ERBB4 isoforms and provide new insight into key biologic and anabolic processes in normal mammary epithelium and breast cancer.

The relationship between tumor-associated macrophages (TAM) and epithelial-to-mesenchymal transition (EMT) during the initiation and progression of metastasis remains unclear. Zhang and colleagues identify that TNFα in macrophage conditioned media inhibits vitamin D receptor (VDR) expression, whereas downregulation of VDR further mediates the promotion of TGFβ-induced EMT by TNFα in breast cancer cells. Furthermore, VDR overexpression inhibits β-catenin, and treatment with 1,25-(OH)2D3 exerts antimetastatic effects in breast cancer with preservation of VDR and suppression of β-catenin. Combined, these results suggest a role for VDR in metastasis, as well as a role in the relationship between TAMs and EMT.