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Updated: Jun 23, 2025
Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor
Published on: September 13, 2018
ACSS2 enables melanoma cell survival and tumor metastasis by negatively regulating the Hippo pathway
Baolu Zhang1, Qing Zhu1, Di Qu1
1Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Introduction:
Acetyl-CoA synthetase 2 (ACSS2), one of the enzymes that catalyze the conversion of acetate to acetyl-CoA, has been proved to be an oncogene in various cancers. However, the function of ACSS2 is still largely a black box in melanoma.
Methods:
The ACSS2 expression was detected in melanoma cells and melanocytes at both protein and mRNA levels. Cell viability, apoptosis, migration and invasion were investigated after ACSS2 knockdown. RNA sequencing (RNA-Seq) technology was employed to identify differentially expressed genes caused by ACSS2 knockdown, which were then verified by immunoblotting analysis. Animal experiments were further performed to investigate the influence of ACSS2 on tumor growth and metastasis in vivo.
Results:
Firstly, we found that ACSS2 was upregulated in most melanoma cell lines compared with melanocytes. In addition, ACSS2 knockdown dramatically suppressed melanoma cell migration and invasion, whereas promoted cell apoptosis in response to endoplasmic reticulum (ER) stress. Furthermore, tumor growth and metastasis were dramatically suppressed by ACSS2 knockdown in vivo. RNA-Seq suggested that the Hippo pathway was activated by ACSS2 knockdown, which was forwardly confirmed by Western blotting and rescue experiments. Taken together, we demonstrated that ACSS2 enables melanoma cell survival and tumor metastasis via the regulation of the Hippo pathway.
Discussion:
In summary, this study demonstrated that ACSS2 may promote the growth and metastasis of melanoma by negatively regulating the Hippo pathway. Targeting ACSS2 may be a promising target for melanoma treatment.
Insights
Acetyl-CoA synthetase 2 (ACSS2) promotes melanoma cell survival and metastasis by inhibiting the Hippo pathway. Inhibiting ACSS2 significantly suppressed tumor growth and spread, suggesting ACSS2 as a potential therapeutic target for melanoma.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Acetyl-CoA synthetase 2 (ACSS2) is implicated as an oncogene in various cancers.
- The specific role of ACSS2 in melanoma pathogenesis remains largely uncharacterized.
Purpose of the Study:
- To investigate the function of ACSS2 in melanoma.
- To elucidate the molecular mechanisms underlying ACSS2's role in melanoma progression.
Main Methods:
- ACSS2 expression analysis in melanoma cell lines and melanocytes.
- Functional assays (viability, apoptosis, migration, invasion) following ACSS2 knockdown.
- RNA sequencing (RNA-Seq) to identify differentially expressed genes.
- In vivo studies to assess tumor growth and metastasis.
- Western blotting and rescue experiments to validate pathway involvement.
Main Results:
- ACSS2 expression is upregulated in most melanoma cell lines.
- ACSS2 knockdown inhibited melanoma cell migration and invasion, and promoted apoptosis.
- Tumor growth and metastasis were significantly suppressed by ACSS2 knockdown in vivo.
- ACSS2 knockdown activated the Hippo pathway, confirmed by molecular analyses.
Conclusions:
- ACSS2 promotes melanoma cell survival and metastasis by negatively regulating the Hippo pathway.
- Targeting ACSS2 represents a potential therapeutic strategy for melanoma treatment.
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