Related Experiment Video

Updated: Mar 19, 2026

Author Spotlight: Unveiling Transmembrane Protein Family-Related Markers in Gastric Cancer and Implications for Targeted Therapies
07:47

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

Published on: September 15, 2023

2.3K

Chromatin remodeling gene AT-rich interactive domain-containing protein 1A suppresses gastric cancer cell

Qian Zhang1, Hai-Bo Yan1, Jie Wang1

  • 1Minhang Hospital and Institutes of Biomedical Sciences, Fudan University, Shanghai 201199, China.

Oncotarget
|June 22, 2016
PubMed

Insights

The tumor suppressor ARID1A (AT-rich interactive domain-containing protein 1A) normally inhibits gastric cancer growth by suppressing PI3K/AKT signaling. Its loss activates this pathway, promoting cancer progression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Signaling

Background:

  • The tumor suppressor AT-rich interactive domain-containing protein 1A (ARID1A) is frequently mutated in various cancers.
  • The precise mechanism by which ARID1A modulates the PI3K/AKT signaling pathway in gastric cancer (GC) remains largely unknown.

Purpose of the Study:

  • To elucidate the role and mechanism of ARID1A in regulating PI3K/AKT signaling in gastric cancer.
  • To investigate the impact of ARID1A deficiency on gastric cancer cell proliferation and tumor growth.

Main Methods:

  • Utilized gene silencing (ARID1A depletion) to assess effects on GC cell proliferation, colony formation, and nutrient uptake in vitro and tumor growth in vivo.
  • Employed phospho-protein antibody arrays to profile PI3K/AKT pathway activation.
  • Conducted chromatin immunoprecipitation and luciferase reporter assays to determine direct transcriptional regulation of PIK3CA and PDK1.
  • Performed serial deletion mutation analyses to identify critical domains of ARID1A involved in its function.

Main Results:

  • ARID1A depletion significantly enhanced gastric cancer cell proliferation, growth, and nutrient uptake in vitro, and promoted xenograft tumor growth in vivo.
  • ARID1A silencing led to increased phosphorylation of key PI3K/AKT pathway components (PDK1, AKT, GSK3β, 70S6K) and elevated protein/mRNA levels of PI3K and PDK1.
  • The SWI/SNF complex, involving ARID1A, directly suppressed PIK3CA and PDK1 transcription by binding to their promoters. The central region of ARID1A was crucial for these inhibitory effects.
  • ARID1A-deficient cells showed sensitivity to PI3K (LY294002) and AKT (mk2206, AT7867) inhibitors, with LY294002 alone inhibiting tumor growth in vivo.

Conclusions:

  • ARID1A functions as a crucial suppressor of gastric cancer progression by inhibiting the PI3K/AKT signaling pathway at the transcriptional level.
  • Loss of ARID1A promotes gastric cancer growth through activation of the PI3K/AKT pathway, highlighting ARID1A as a potential therapeutic target.
Keywords:
ARID1APDK1PIK3CASWI/SNF complexgastric cancer

More Related Videos

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

7.5K
Author Spotlight: Genetic Profiling for Fluorouracil Response in Gastric Cancer06:21

Author Spotlight: Genetic Profiling for Fluorouracil Response in Gastric Cancer

Published on: May 10, 2024

1.4K

Related Concept Videos

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
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...
6.1K
Inhibition of CDK Activity02:34

Inhibition of CDK Activity

5.6K
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...
5.0K
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...
6.2K
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...
13.7K