Related Experiment Video

Updated: Dec 21, 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

2.1K

SH3RF3 promotes breast cancer stem-like properties via JNK activation and PTX3 upregulation

Peiyuan Zhang1,2, Yingjie Liu1,2, Cheng Lian1

  • 1Shanghai Institute of Nutrition and Health, Shanghai Jiao Tong University School of Medicine (SJTUSM) & Chinese Academy of Sciences, Shanghai, China.

Nature Communications
|May 20, 2020
PubMed

Insights

A newly identified scaffold protein, SH3RF3, promotes breast cancer stem cell properties by activating the JNK-JUN pathway. This finding offers potential new therapeutic targets for combating cancer recurrence and metastasis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Cancer stem-like cells (CSCs) drive tumor recurrence and metastasis.
  • Regulatory mechanisms governing CSCs are not fully understood.
  • Identifying novel CSC regulators is crucial for developing targeted therapies.

Purpose of the Study:

  • To identify and characterize novel regulators of breast cancer stem cells (CSCs).
  • To elucidate the molecular mechanism by which SH3RF3 influences CSC properties.
  • To explore the therapeutic potential of targeting SH3RF3 in breast cancer.

Main Methods:

  • Transcriptomic analysis to identify upregulated genes in CSCs.
  • Functional assays to assess the impact of SH3RF3 on CSC properties.
  • Co-immunoprecipitation and Western blotting to investigate protein interactions and signaling pathways.
  • Patient-derived organoid cultures and clinical cohort analyses for validation.

Main Results:

  • SH3RF3 (POSH2) is upregulated in breast cancer CSCs and enhances CSC characteristics.
  • SH3RF3 interacts with JNK in a JIP-dependent manner, activating the JNK-JUN pathway.
  • The JNK-JUN pathway, activated by SH3RF3, upregulates PTX3, expanding the CSC subpopulation.
  • SH3RF3's role in CSCs is confirmed in patient-derived organoids and clinical data.

Conclusions:

  • SH3RF3 is a key regulator of breast cancer stem cells.
  • SH3RF3 promotes CSC properties through the JNK-JUN-PTX3 signaling axis.
  • SH3RF3 represents a potential therapeutic target for breast cancer treatment, aiming to reduce recurrence and metastasis.

More Related Videos

Isolation and Functional Assessment of Human Breast Cancer Stem Cells from Cell and Tissue Samples07:03

Isolation and Functional Assessment of Human Breast Cancer Stem Cells from Cell and Tissue Samples

Published on: October 2, 2020

4.9K
Three-Dimensional 3D Tumor Spheroid Invasion Assay12:19

Three-Dimensional 3D Tumor Spheroid Invasion Assay

Published on: May 1, 2015

59.1K

Related Concept Videos

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...
4.5K
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
11.5K
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...
5.1K
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...
5.0K
Cancer Stem Cells and Tumor Maintenance02:40

Cancer Stem Cells and Tumor Maintenance

Early diagnosis and treatment can often cure cancer. However, even with treatment, residual cells called cancer stem cells (CSC) might remain, often causing tumor recurrence. These cancer stem cells possess the potential for self-renewal and multi-lineage differentiation and are often responsible for the therapeutic resistance displayed in most cancers.
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...
5.8K
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...
7.7K