Related Experiment Video
Updated: Mar 11, 2026
All-optical Mechanobiology Interrogation of Yes-associated Protein in Human Cancer and Normal Cells using a Multi-functional System
Published on: December 20, 2021
YAP1 regulates ABCG2 and cancer cell side population in human lung cancer cells
Yuyuan Dai1, Shu Liu1, Wen-Qian Zhang1,2
1Thoracic Oncology Laboratory, Department of Surgery, Comprehensive Cancer Center, University of California, San Francisco, CA, USA.
Abstract:
A small population of cancer cells called cancer-initiating cells or cancer stem cells (CSCs) are involved in drug resistance, metastasis, and cancer relapse. Finding pathways that regulate CSC is very important for clinical therapy. ATP-binding cassette sub-family G member 2 (ABCG2) plays a role in side population (SP) cell formation and contributes to chemotherapy resistance in common forms of cancer. Yes-associated protein 1 (YAP1) is a major transcriptional effector of the Hippo pathway, which plays important roles in organ size control and tumorigenesis. In this study, we found ABCG2 and YAP1 were both overexpressed in lung cancer SP cells. Disruption of YAP1 expression by siRNA attenuated the expression of ABCG2 transcript and significantly reduced the percentage of SP cells and sphere formation in lung cancer cells. Overexpression of YAP1 in lung cancers led to an increase in ABCG2 expression and increased the percentage of SP cells. However, overexpression of YAP1 in purified non-SP cells did not increase ABCG2 expression and the percentage of SP cells, which may be due to the inhibition of YAP activity through phosphorylation. YAP1 directly transcriptionally regulated ABCG2 by binding to the promoter of ABCG2. Moreover, the YAP1 inhibitor verteporfin and YAP1 siRNA downregulated ABCG2 level through inhibition of YAP1 in lung cancer cells and sensitized them to the chemotherapy drug doxorubicin. Our study adds a new function for YAP1 that may be relevant to drug resistance and cancer therapy through regulation of ABCG2 and side population cell formation in lung cancer.
Insights
Cancer stem cells (CSCs) drive drug resistance. This study reveals Yes-associated protein 1 (YAP1) regulates ATP-binding cassette sub-family G member 2 (ABCG2) in lung cancer, offering new therapeutic targets.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Stem Cell Research
Background:
- Cancer stem cells (CSCs) are implicated in drug resistance, metastasis, and relapse.
- ATP-binding cassette sub-family G member 2 (ABCG2) is crucial for side population (SP) cell formation and chemotherapy resistance.
- Yes-associated protein 1 (YAP1) is a key effector of the Hippo pathway, involved in organ size control and tumorigenesis.
Purpose of the Study:
- To investigate the role of YAP1 in regulating ABCG2 expression and CSC properties in lung cancer.
- To elucidate the mechanism by which YAP1 influences ABCG2 and CSCs.
- To evaluate the therapeutic potential of targeting the YAP1-ABCG2 axis for overcoming drug resistance.
Main Methods:
- Quantitative analysis of ABCG2 and YAP1 expression in lung cancer SP cells.
- Gene silencing using siRNA to disrupt YAP1 expression.
- Overexpression studies of YAP1 in lung cancer cells.
- Analysis of SP cell percentage and sphere formation.
- Chromatin immunoprecipitation (ChIP) to assess YAP1 binding to the ABCG2 promoter.
- Treatment with YAP1 inhibitor (verteporfin) and chemotherapy drug (doxorubicin).
Main Results:
- Both ABCG2 and YAP1 were overexpressed in lung cancer SP cells.
- YAP1 disruption reduced ABCG2 expression, SP cell percentage, and sphere formation.
- YAP1 overexpression increased ABCG2 expression and SP cell percentage.
- YAP1 directly bound to the ABCG2 promoter, indicating transcriptional regulation.
- YAP1 inhibition sensitized lung cancer cells to doxorubicin.
Conclusions:
- YAP1 directly regulates ABCG2 expression in lung cancer.
- The YAP1-ABCG2 pathway contributes to CSC properties and drug resistance.
- Targeting YAP1 offers a potential strategy to enhance chemotherapy efficacy in lung cancer.
More Related Videos
10:32Combined 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
09:57Harnessing the DNA Dye-triggered Side Population Phenotype to Detect and Purify Cancer Stem Cells from Biological Samples
Published on: May 10, 2017
Related Concept Videos
02:23Abnormal Proliferation
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
02:50Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
02:53Adaptive Mechanisms in Cancer Cells
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
01:20The Retinoblastoma Gene
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...