Regulation of Numb isoform expression by activated ERK signaling
ONCOGENE
Authors: Rajendran, D.; Zhang, Y.; Berry, D. M.; McGlade, C. J.
Abstract
The endocytic adaptor protein Numb has a major role in development as an intrinsic regulator of cell fate determination and inhibitor of the Notch signaling pathway. In vertebrates, four protein isoforms of Numb are produced through alternative splicing (AS) of two cassette exons (exons 3 and 9). AS of coding exon 9 (E9) produces E9-included (p72/p71) and -excluded (p66/p65) protein products. Expression of Numb isoforms is developmentally regulated and E9-included products are expressed in progenitors, whereas E9-excluded isoforms are dominantly expressed in differentiated cells. Analyses of AS events in multiple cancers previously identified a switch in Numb transcript and protein expression from the E9-excluded to the E9-included isoform, suggesting that misregulation of the mechanisms that control E9 inclusion may have a role in tumorigenesis. Here we identify splicing factors ASF/SF2 and PTBP1 as regulators of E9 splicing and show that activation of the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway promotes E9 inclusion in cancer cells. Our evidence supports a mechanism by which Numb AS is regulated in response to oncogenic signaling pathways, and contributes to activation of downstream pathways to promote tumorigenesis.
Reflecting a crisis reaction: Narratives from patients with oesophageal cancer about the first 6 months after diagnosis and surgery
NURSING OPEN
Authors: Hellstadius, Ylva; Malmstrom, Marlene; Lagergren, Pernilla; Sundbom, Magnus; Wikman, Anna
Abstract
Aim The aim of the study was to describe patients' experiences of emotional adaption following treatment for oesophageal cancer from diagnosis to 6 months after surgery. Design A qualitative interview study using an inductive approach was carried out. Methods Participants were recruited from two university hospitals in Sweden. Ten patients who had been operated for oesophageal cancer with curative intent 6 months earlier and consented to participate in the study were included. Patients who had a disease recurrence were not eligible for inclusion. Participants were interviewed with a semi-structured interview approach. Data were analysed using qualitative content analysis. Results One overarching theme was identified; Experiencing a crisis reaction, which comprised three key categories; (a) From emotionally numb to feeling quite alright; (b) From a focus on cure to reflections about a whole new life; and (c) From a severe treatment to suffering an emaciated, non-compliant body, derived from 14 distinct sub-categories. Conclusion This study highlights the process of emotional adaptation following oesophageal cancer surgery that patients describe when reflecting back on the first 6 months postoperatively pointing to a crisis reaction in this early postoperative period.