Related Experiment Video

Updated: Sep 24, 2025

Author Spotlight: Exploring Salidroside's Molecular Mechanisms in Breast Cancer Treatment
11:13

Author Spotlight: Exploring Salidroside's Molecular Mechanisms in Breast Cancer Treatment

Published on: June 9, 2023

1.7K

Physiological expression of PI3K H1047R mutation reveals its anti-metastatic potential in ErbB2-driven breast cancer

Alexandra M Simond1,2, Tung Bui1,2, Dongmei Zuo1

  • 1Rosalind and Morris Goodman Cancer Research Institute, McGill University, Montreal, QC, Canada.

Oncogene
|May 10, 2022
PubMed

Insights

Activating mutations in p110α, common in breast cancer, surprisingly reduce lung metastasis when combined with ErbB2. This is linked to decreased cellular contractility and myosin light chain 2 activity.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Genetics

Background:

  • Phosphoinositide 3-kinase (PI3K) p110α is a key downstream effector of receptor tyrosine kinase ErbB2.
  • PIK3CA gain-of-function mutations are frequent in breast cancer, but their prognostic significance remains debated.
  • ErbB2 amplification and p110α overexpression occur in 20-30% of breast cancers.

Purpose of the Study:

  • To investigate the impact of an activated ErbB2 and p110α kinase domain mutation (p110αHR) on breast cancer progression and metastasis using a knock-in transgenic model.
  • To explore the molecular mechanisms underlying metastasis and cellular contractility in ErbB2-driven breast cancer with p110αHR mutations.

Main Methods:

  • Generation of a bi-genic transgenic mouse model expressing activated ErbB2 and p110αHR in the mammary epithelium under endogenous promoter control.
  • Analysis of tumor development, metastatic capacity (lung metastasis), and myoepithelial layer integrity.
  • Molecular and biochemical assays to assess phospho-myosin light chain 2 (MLC2) levels, cellular contractility, and migration.

Main Results:

  • Tumors in the ErbB2/p110αHR bi-genic mice showed significantly reduced lung metastasis compared to ErbB2-only tumors.
  • Reduced metastasis was associated with the retention of the myoepithelial layer, resembling non-invasive ductal carcinoma in situ (DCIS).
  • These tumors displayed decreased phospho-MLC2, indicating reduced cellular contractility and migration.

Conclusions:

  • The p110αHR mutation attenuates metastatic behavior in ErbB2-driven breast cancer.
  • Decreased cellular contractility and MLC2 activity contribute to the reduced metastatic potential.
  • Progressive increase in cellular contractility observed from DCIS to invasive ductal carcinoma in human samples supports these findings.

More Related Videos

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer06:51

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

18.1K
Author Spotlight: Unveiling Transmembrane Protein Family-Related Markers in Gastric Cancer and Implications for Targeted Therapies07:47

Author Spotlight: Unveiling Transmembrane Protein Family-Related Markers in Gastric Cancer and Implications for Targeted Therapies

Published on: September 15, 2023

1.7K

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...
4.1K
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...
3.9K
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...
4.6K
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
7.0K
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...
6.6K
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...
6.5K