Related Experiment Video

Updated: Mar 28, 2026

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer
06:51

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer

Published on: July 21, 2018

18.8K

Activated mutant forms of PIK3CA cooperate with RasV12 or c-Met to induce liver tumour formation in mice via

Chunmei Wang1, Li Che1,2, Junjie Hu1,3

  • 1Department of Bioengineering and Therapeutic Sciences and Liver Center, University of California, San Francisco, CA, USA.

Liver International : Official Journal of the International Association for the Study of the Liver
|December 31, 2015
PubMed
Abstract

Insights

Activating PIK3CA mutations promote liver cancer when combined with NRasV12 or c-Met, requiring the AKT2/mTOR pathway for tumor formation.

Area of Science:

  • Oncology
  • Molecular Biology
  • Hepatology

Background:

  • Activating mutations in PIK3CA are found in various cancers, including hepatocellular carcinoma.
  • The precise role of PIK3CA in liver cancer development (hepatocarcinogenesis) is not fully understood.
  • Investigating PIK3CA's contribution to liver tumorigenesis is crucial for understanding cancer mechanisms.

Purpose of the Study:

  • To elucidate the mechanisms by which PIK3CA mutations contribute to hepatocellular carcinoma.
  • To determine the role of specific PIK3CA mutants (H1047R, E545K) in liver cancer initiation and progression.
  • To identify key signaling pathways involved in PIK3CA-driven hepatocarcinogenesis.

Main Methods:

  • Hydrodynamic transfection of PIK3CA mutants (H1047R, E545K) into mouse liver, alone or with NRasV12 or c-Met.
  • Analysis of AKT/mTOR and Ras/MAPK signaling pathway activation.
  • Assessment of tumor formation, hepatic steatosis, and gene knockout models (AKT2, Raptor) to study pathway requirements.

Main Results:

  • PIK3CA mutants alone induced AKT/mTOR signaling and hepatic steatosis but not tumors.
  • Co-expression of PIK3CA mutants with NRasV12 or c-Met rapidly led to liver tumor formation.
  • AKT/mTOR and Ras/MAPK pathways were activated in all tumors; AKT2 ablation inhibited steatosis and carcinogenesis.

Conclusions:

  • PIK3CA mutants H1047R and E545K activate the AKT/mTOR pathway.
  • The AKT2/mTOR complex 1 cascade is essential for PIK3CA-mutant-driven liver tumor formation when cooperating with c-Met.
  • Cooperative signaling between PIK3CA and other oncogenes drives hepatocarcinogenesis.
Keywords:
AKT/mTORNRasV12PIK3CA mutantsc-Metliver cancer

More Related Videos

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods07:49

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods

Published on: July 17, 2019

6.6K
Initiation of Metastatic Breast Carcinoma by Targeting of the Ductal Epithelium with Adenovirus-Cre: A Novel Transgenic Mouse Model of Breast Cancer07:13

Initiation of Metastatic Breast Carcinoma by Targeting of the Ductal Epithelium with Adenovirus-Cre: A Novel Transgenic Mouse Model of Breast Cancer

Published on: March 26, 2014

24.1K

Related Concept Videos

PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
6.3K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
5.1K
The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...
7.5K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
9.2K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.4K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
7.9K