Functional compensation between Myc and PI3K signaling supports self-renewal of embryonic stem cells.

Stem Cells

Division of Developmental Biology, Research Center for Genomic Medicine, Saitama Medical University, Yamane, Hidaka, Saitama, Japan; Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency, Kawaguchi, Saitama, Japan; Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, California, USA.

Published: March 2015

AI Article Synopsis

  • c-Myc and phosphatidylinositol 3-OH kinase (PI3K) play key roles in cell cycle regulation and maintaining embryonic stem cell (ESC) characteristics, but their specific relationship in ESCs is not fully understood.
  • Research shows that c-Myc and PI3K work together yet separately to help sustain the self-renewal of murine ESCs in standard culture conditions.
  • When ESCs are cultured in a specific 2i-condition, which includes inhibitors for GSK3β and MEK, the need for c-Myc and PI3K signaling for maintaining pluripotency decreases, indicating that their roles are context-dependent.

Article Abstract

c-Myc and phosphatidylinositol 3-OH kinase (PI3K) both participate in diverse cellular processes, including cell cycle control and tumorigenic transformation. They also contribute to preserving embryonic stem cell (ESC) characteristics. However, in spite of the vast knowledge, the molecular relationship between c-Myc and PI3K in ESCs is not known. Herein, we demonstrate that c-Myc and PI3K function cooperatively but independently to support ESC self-renewal when murine ESCs are cultured under conventional culture condition. Interestingly, culture of ESCs in 2i-condition including a GSK3β and MEK inhibitor renders both PI3K and Myc signaling dispensable for the maintenance of pluripotent properties. These results suggest that the requirement for an oncogenic proliferation-dependent mechanism sustained by Myc and PI3K is context dependent and that the 2i-condition liberates ESCs from the dependence of this mechanism.

Download full-text PDF

Source
http://dx.doi.org/10.1002/stem.1893DOI Listing

Publication Analysis

Top Keywords

myc pi3k
8
embryonic stem
8
c-myc pi3k
8
pi3k
6
functional compensation
4
compensation myc
4
pi3k signaling
4
signaling supports
4
supports self-renewal
4
self-renewal embryonic
4

Similar Publications

Embryonic-type neuroectodermal tumors (ENTs) arising from testicular germ cell tumors (GCTs) is a relatively common type of somatic transformation in GCTs with poor prognosis and limited therapeutic options, particularly when patients develop disease recurrence or metastasis. Knowledge of key events driving this transformation is limited to the paucity of comprehensive genomic data. We performed a retrospective database search in a CLIA- and CAP-certified laboratory for testicular GCT-derived ENTs that had previously undergone NGS-based comprehensive genomic profiling during the course of clinical care.

View Article and Find Full Text PDF

Background And Objective: Prostate cancer is a major cause of cancer-related morbidity and mortality in men globally. The pathogenesis involves complex interactions between genetic mutations and environmental factors, activating multiple signaling pathways, especially Wnt/β-catenin, PI3K/Akt, and NF-κB pathways. Tumor suppressor genes and are key inhibitors of these pathways, crucial in suppressing tumor growth and metastasis.

View Article and Find Full Text PDF

Pancreatic cancer is characterized by severe metabolic stress due to its prominent desmoplasia and poor vascularization. Integrin subunit alpha 3 (ITGA3) is a cell surface adhesion protein involved in tumor progression. However, the role of ITGA3 in pancreatic cancer progression, especially in metabolic reprogramming, remains largely unknown.

View Article and Find Full Text PDF

ATPase family AAA domain-containing protein 2 (ATAD2) is significantly up-regulated in many cancer types and contributes to poor patient outcomes. ATAD2 exhibits a multidomain architecture comprising an N-terminal acidic domain, two AAA+ ATPase domains, a bromodomain, and a C-terminal domain. The AAA+ ATPase domain facilitates protein oligomerization and ATP binding, while the bromodomain recognizes acetylated lysine in histones and nonhistone proteins.

View Article and Find Full Text PDF

Background: Approximately 30% of the non-small cell lung cancer (NSCLC) patients which harbor no recognizable oncogenic driver mutation are not eligible for targeted therapy. Functional drug screening of tumor cells helps to identify susceptible drug targets not recognized by gene panels for targeted mutation analysis. The aim of this study is to characterize the BH1406 cell line carrying an activating SOS1 mutation and to check its sensitivity to cognate inhibitors.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!