Related Experiment Video

Updated: Oct 7, 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

1.8K

MAPK4 promotes triple negative breast cancer growth and reduces tumor sensitivity to PI3K blockade

Wei Wang1, Dong Han1, Qinbo Cai1

  • 1Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.

Nature Communications
|January 12, 2022
PubMed

Insights

High MAPK4 expression drives triple-negative breast cancer (TNBC) growth by activating AKT independently of PI3K. Targeting MAPK4 offers a new therapeutic strategy for TNBC, enhancing sensitivity to PI3K inhibitors.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Signaling Pathways

Background:

  • Triple-negative breast cancer (TNBC) accounts for 15-20% of breast cancers and has limited treatment options.
  • PI3K/PTEN pathway aberrations are frequent in TNBC, yet PI3K inhibitors show limited efficacy.
  • The mechanisms behind the limited therapeutic impact of PI3K inhibitors in TNBC are not fully understood.

Purpose of the Study:

  • To investigate the role of MAPK4 in TNBC pathogenesis.
  • To explore MAPK4 as a potential therapeutic target in TNBC.
  • To understand how MAPK4 influences AKT activation and sensitivity to PI3K inhibition.

Main Methods:

  • Analysis of MAPK4 expression in TNBC subsets.
  • Investigating the functional role of MAPK4 in TNBC cell proliferation and xenograft growth.
  • Evaluating the combined effect of MAPK4 repression and PI3K inhibition on TNBC.

Main Results:

  • A significant subset of TNBC expresses high levels of MAPK4.
  • MAPK4 drives AKT activation independently of PI3K, promoting TNBC growth.
  • Repressing MAPK4 sensitizes TNBC cells and xenografts to PI3K blockade.

Conclusions:

  • High MAPK4 expression identifies a TNBC subset responsive to MAPK4 inhibition.
  • Targeting MAPK4 can repress TNBC growth and sensitize tumors to PI3K inhibitors.
  • MAPK4 acts as a critical regulator of AKT activation, bypassing PI3K in TNBC.

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
Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts10:27

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts

Published on: July 25, 2020

7.4K

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
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
5.0K
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
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...
4.7K
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...
6.4K