Related Experiment Video

Updated: Jul 16, 2026

Induction of Invasive Transitional Cell Bladder Carcinoma in Immune Intact Human MUC1 Transgenic Mice: A Model for Immunotherapy Development
11:02

Induction of Invasive Transitional Cell Bladder Carcinoma in Immune Intact Human MUC1 Transgenic Mice: A Model for Immunotherapy Development

Published on: October 30, 2013

Oncogenic PIK3CA reprograms glutamine metabolism to drive bladder cancer progression

Karthik Reddy Kami Reddy1,2, Vasanta Putluri3,4, Danthasinghe Waduge Badrajee Piyarathna5

  • 1Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas, USA. karthikr@bcm.edu.

Cell Communication and Signaling : CCS
|July 15, 2026
PubMed
Abstract

Insights

PIK3CA mutations in bladder cancer reprogram metabolism, increasing glutamine use and fatty acid synthesis to drive tumor growth. These metabolic changes offer new therapeutic targets for aggressive PIK3CA-mutant bladder cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Metabolic Research

Background:

  • Genomic analysis reveals PI3K/AKT pathway alterations in ~40% of bladder cancer (BLCA).
  • PIK3CA mutations occur in 15-25% of BLCA, encoding a key regulator of cell survival and metabolism.
  • The metabolic impact of PIK3CA mutations in BLCA is not well understood.

Purpose of the Study:

  • To investigate the metabolic and functional consequences of PIK3CA mutations in BLCA.
  • To identify potential therapeutic targets for PIK3CA-mutant BLCA.

Main Methods:

  • Targeted sequencing of patient tumors and CRISPR/Cas9 knock-in models.
  • Transcriptomic profiling, metabolomics, and stable isotope tracing.
  • Functional assays for proliferation, mitochondrial activity, and glutaminolysis; in vivo xenograft studies.

Main Results:

  • PIK3CA mutations (E545K/Q hotspots) activate PI3K/AKT signaling, altering metabolism.
  • Increased OXPHOS, fatty acid metabolism, and mTORC1 signaling observed.
  • Enhanced glutamine metabolism to citrate, increased fatty acid synthesis, proliferation, and mitochondrial activity in mutant cells; accelerated tumor growth in vivo.

Conclusions:

  • PIK3CA mutations drive metabolic reprogramming in BLCA, promoting tumor progression via glutamine flux and fatty acid synthesis.
  • Metabolic alterations serve as biomarkers for aggressive disease and potential therapeutic targets.
  • Targeting PI3Kα and metabolic pathways offers precision medicine strategies for PIK3CA-mutant BLCA.

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