Related Experiment Video

Updated: Dec 18, 2025

Combined Use of Tail Vein Metastasis Assays and Real-Time In Vivo Imaging to Quantify Breast Cancer Metastatic Colonization and Burden in the Lungs
10:32

Combined Use of Tail Vein Metastasis Assays and Real-Time In Vivo Imaging to Quantify Breast Cancer Metastatic Colonization and Burden in the Lungs

Published on: December 19, 2019

11.4K

SASH1 suppresses triple-negative breast cancer cell invasion through YAP-ARHGAP42-actin axis

Ke Jiang1, Peng Liu2,3, Huizhe Xu1

  • 1Institute of Cancer Stem Cell, Dalian Medical University Cancer Center, 116044, Dalian, China.

Oncogene
|June 12, 2020
PubMed

Insights

Triple-negative breast cancer (TNBC) progression is linked to low SASH1 levels. Restoring SASH1 suppresses invasion by regulating the Hippo-YAP pathway, offering a potential therapeutic target for aggressive TNBC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Triple-negative breast cancer (TNBC) is an aggressive subtype lacking effective therapies.
  • SAM and SH3 domain containing 1 (SASH1) is a potential tumor suppressor in TNBC, but its mechanisms are unclear.
  • SASH1 is significantly downregulated in TNBC compared to other breast cancer subtypes.

Purpose of the Study:

  • To elucidate the mechanism of SASH1's tumor-suppressive activity in TNBC.
  • To investigate the role of SASH1 in regulating TNBC cell invasion and the Hippo-YAP pathway.
  • To identify SASH1 as a potential therapeutic target for TNBC.

Main Methods:

  • Analysis of SASH1 expression in TNBC patient samples.
  • In vitro studies using TNBC cell lines with SASH1 ectopic expression or depletion.
  • In vivo validation using chicken chorioallantoic membrane and mouse xenograft models.
  • Investigation of the Hippo-YAP signaling pathway, including LATS1, YAP, CYR61, and ARHG42.
  • Pharmacological inhibition and knockdown of YAP.
  • Site-directed mutagenesis of SASH1 (S407A mutant).

Main Results:

  • SASH1 depletion enhanced TNBC cell invasion, correlating with increased MMP2 and MMP9 expression.
  • SASH1 knockdown led to decreased LATS1 phosphorylation and increased YAP accumulation, upregulating YAP targets like CYR61 and ARHG42.
  • Inhibition or knockdown of YAP reversed the invasive phenotype induced by SASH1 depletion.
  • SASH1-regulated YAP signaling was LATS1-dependent, with SASH1 phosphorylation influencing this interaction.
  • The YAP-ARHG42-actin axis was identified as a key mediator of SASH1-regulated TNBC cell invasion.

Conclusions:

  • SASH1 acts as a tumor suppressor in TNBC by inhibiting cell invasion.
  • SASH1 regulates TNBC cell invasion through the LATS1-YAP-ARHG42 axis.
  • Targeting SASH1 or the downstream YAP pathway presents a potential therapeutic strategy for TNBC.

More Related Videos

All-optical Mechanobiology Interrogation of Yes-associated Protein in Human Cancer and Normal Cells using a Multi-functional System09:55

All-optical Mechanobiology Interrogation of Yes-associated Protein in Human Cancer and Normal Cells using a Multi-functional System

Published on: December 20, 2021

3.3K
Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter11:32

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter

Published on: March 27, 2020

7.3K

Related Concept Videos

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...
11.4K
Cancer Cell Migration through Invadopodia01:35

Cancer Cell Migration through Invadopodia

Invadosome is a broad category of cell surface structures with proteolytic activity that  degrades the extracellular matrix (ECM). Invadosomes are present in normal cell types, including macrophages, endothelial cells, and neurons, as well as tumor cells. Although the macrophage podosomes and tumor cell invadopodia are classified as invadosomes, they have different structures, molecular pathways, and functions. Podosomes are short structures that last for a few minutes. However,...
3.1K
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
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...
7.1K
Anaphase Promoting Complex00:50

Anaphase Promoting Complex

The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
3.2K
Separation of Sister Chromatids02:17

Separation of Sister Chromatids

At the transition from prophase to metaphase, there is a reduction in cohesion along the chromosomal arms, resulting in the resolution of sister chromatids. However, residual cohesin connections remain to hold the sister chromatids together until the transition from metaphase to anaphase. The residual connection prevents any premature separation of sister chromatids, blocking the risks of aneuploidy within the daughter cells.
At the onset of anaphase, separase, a proteolytic enzyme, is...
4.2K