# ESCO2 promotes the proliferation of hepatocellular carcinoma through the PI3K/AKT/ mTOR signaling pathway

**Authors:** Dapeng Chen, Yue Huang, Weixin Zhang, Youcheng Zhang, Yi Bai, Yamin Zhang

PMC · DOI: 10.7150/jca.112087 · Journal of Cancer · 2025-06-23

## TL;DR

ESCO2 promotes liver cancer growth by activating the PI3K/AKT/mTOR pathway, which speeds up cell division and prevents cell death.

## Contribution

This study identifies ESCO2 as a driver of hepatocellular carcinoma proliferation through the PI3K/AKT/mTOR signaling pathway.

## Key findings

- ESCO2 is significantly upregulated in hepatocellular carcinoma tissues and is associated with poor prognosis.
- Knockdown of ESCO2 inhibits HCC cell proliferation in both in vitro and in vivo models.
- ESCO2 activates the PI3K/AKT/mTOR pathway, promoting cell cycle progression and suppressing apoptosis.

## Abstract

Background: Establishment of sister chromatid cohesion N-Acetyltransferase 2 (ESCO2) is a gene implicated in the establishment of sister chromatid cohesion (SCC) and cell proliferation. We aimed to explore how ESCO2 affects the proliferation of hepatocellular carcinoma (HCC).

Methods: We analyzed ESCO2 expression levels and their association with clinical prognosis using the TCGA, HCCDB, and ICGC databases. Bioinformatics methods were employed to investigate potential regulatory pathways involving ESCO2. CCK-8 assays, colony formation assays, and flow cytometry were used to examine the impact of ESCO2 knockdown on the malignant biological behavior of HCC cells. Western blotting was utilized to identify the specific regulatory mechanism of ESCO2.

Results:
ESCO2 was significantly upregulated in HCC tissues and correlated with a worse prognosis. Bioinformatics analysis revealed that ESCO2 regulated pathways related to the cell cycle and cell proliferation. Furthermore, knockdown of ESCO2 significantly inhibited HCC cell proliferation both in vivo and in vitro. Most importantly, ESCO2 stimulated the PI3K/AKT/mTOR pathway, which ultimately accelerated the cell cycle and inhibited apoptosis, promoting HCC progression.

Conclusion: The present study elucidated the mechanism by which ESCO2 regulates HCC proliferation: ESCO2 promotes HCC proliferation by accelerating the cell cycle and inhibiting apoptosis via the PI3K/AKT/mTOR signaling pathway.

## Linked entities

- **Genes:** ESCO2 (establishment of sister chromatid cohesion N-acetyltransferase 2) [NCBI Gene 157570]
- **Proteins:** PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha), AKT1 (AKT serine/threonine kinase 1), MTOR (mechanistic target of rapamycin kinase)
- **Diseases:** hepatocellular carcinoma (MONDO:0007256)

## Full-text entities

- **Genes:** MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, NAT2 (N-acetyltransferase 2) [NCBI Gene 10] {aka AAC2, NAT-2, PNAT}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, ESCO2 (establishment of sister chromatid cohesion N-acetyltransferase 2) [NCBI Gene 157570] {aka 2410004I17Rik, EFO2, EFO2p, JHS, RBS, hEFO2}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}
- **Diseases:** HCC (MESH:D006528)
- **Cell lines:** CCK-8 — Homo sapiens (Human), Colon adenocarcinoma, Cancer cell line (CVCL_2873)

## Full text

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## Figures

9 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12244334/full.md

## References

44 references — full list in the complete paper: https://tomesphere.com/paper/PMC12244334/full.md

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Source: https://tomesphere.com/paper/PMC12244334