Research Highlights

Short, accessible synopses of recent important articles concerning signalling pathways.

September 2012

• Micrornas: Lines of communication

  

  Although pharmacological inhibitors of vascular endothelial growth factor (VEGF) signalling and angiogenesis are used in the treatment of many cancers, resistance often develops and therefore it would be desirable to find other non-VEGF pathways that might be exploited therapeutically. Guanglei Zhuang, Napoleone Ferrara and colleagues have identified a role for activation of the Janus kinase (JAK)–signal transducer and activator of transcription (STAT) pathway in endothelial cells by tumour cell-derived microRNAs (miRNAs).

  Original research paper Nature Reviews Cancer 12 580 doi:10.1038/nrc3348

• Migration: VEGF suppresses invasion

  

  Inhibition of vascular endothelial growth factor (VEGF) provides some initial benefit for patients with glioblastoma, but most tumours progress while on this therapy: Gabriele Bergers and colleagues asked why.

  Original research paper Nature Reviews Cancer 12 581 doi:10.1038/nrc3345

• Therapeutics: Holding JAK back

  

  Janus kinase 2 (JAK2) is commonly activated by somatic mutations in myeloproliferative neoplasm (MPN). However, JAK2 inhibitors have only limited effectiveness in treating patients with MPN, and a new study might now explain why: inhibited JAK2 can form heterodimers with other kinases to maintain oncogenic signalling.

  Original research paper Nature Reviews Cancer 12 583 doi:10.1038/nrc3357

• Cell signalling: A necrosome build-up

  

  Receptor-interacting protein 1 (RIP1; also known as RIPK1) can control several crucial cellular functions, including cell survival downstream of nuclear factor-κΒ (NF-κΒ) signalling, apoptosis and programmed necrosis. Here, Wu and colleagues report that RIP1 interacts with RIP3 to form an amyloid-like fibrillar complex that is key in the initiation of programmed necrosis.

  Original research paper Nature Reviews Molecular Cell Biology 13 540 doi:10.1038/nrm3415

• Tumour immunology: TIM3 suppresses antitumour DCs

  

  T cell membrane protein 3 (TIM3) is an immune checkpoint receptor that suppresses the activation of T helper 1 (T_H1) cells on engagement with ligand. It is also expressed by dendritic cells (DCs), which are part of the innate immune system that respond to tumour-derived stress-related factors. The function of TIM3 in innate antitumour immune responses is unclear.

  Original research paper Nature Reviews Immunology 12 620 doi:10.1038/nri3288