CBX1 is involved in hepatocellular carcinoma progression and resistance to sorafenib and lenvatinib via IGF-1R/AKT/SNAIL signaling pathway

Sep 21, 2026

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Chromobox Homolog 1 (CBX1) is examined for its contribution to cancer biology, focusing on hepatocellular carcinoma (HCC) and its relationship to treatment failure. Bioinformatics analyses define CBX1 expression patterns and links to tumor stage and patient outcomes, complemented by single-cell RNA sequencing. Experiments quantify CBX1 in HCC and adjacent tissues using RT-PCR, Western blotting, and immunohistochemistry, while tissue microarrays connect CBX1 with prognosis and clinicopathological features. Functional assays and xenografts show CBX1 modulates proliferation, invasion, migration, EMT, and resistance to sorafenib/lenvatinib through the IGF-1R/AKT/SNAIL axis.

LanguageEnglish

CategoryHealthcare

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Pages17

Reading Time43 min

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Abstract

Methods

Results

Conclusions

Introduction

Hepatology International (2024) 18:1499–1515 [https://doi.org/10.1007/s12072-024-10696-0](https://doi.org/10.1007/s12072-024-10696-0) CBX1 is involved in hepatocellular carcinoma progression and resistance to sorafenib and lenvatinib via IGF‑1R/AKT/SNAIL signaling pathway Su‑Su Zheng1 · Jing‑Fang Wu2 · Wei‑Xun Wu3 · Jin‑Wu Hu4 · Dai Zhang2 · Cheng Huang6 · Bo‑Heng Zhang1,2,5 Received: 17 December 2023 / Accepted: 29 April 2024 / Published online: 20 May 2024 © The Author(s) 2024 Abstract Background Chromobox Homolog 1 (CBX1) plays a crucial role in the pathogenesis of numerous diseases, including the evolution and advancement of diverse cancers. The role of CBX1 in pan-cancer and its mechanism in hepatocellular carcinoma (HCC), however, remains to be further investigated. Methods Bioinformatics approaches were harnessed to scrutinize CBX1’s expression profile, its association with tumor staging, and its potential impact on patient outcomes across various cancers. Single-cell RNA sequencing data facilitated the investigation of CBX1 expression patterns at the individual cell level. The CBX1 expression levels in HCC and adjacent non-tumor tissues were quantified through Real-Time Polymerase Chain Reaction (RT-PCR), Western Blotting (WB), and Immunohistochemical analyses. A tissue microarray was employed to explore the relationship between CBX1 levels, patient prognosis, and clinicopathological characteristics in HCC. Various in vitro assays—including CCK-8, colony formation, Transwell invasion, and scratch tests—were conducted to assess the proliferative and motility properties of HCC cells upon modulation ofCBX1 expression. Moreover, the functional impact ofCBX1 on HCC was further discerned through xenograft studies in nude mice. Results CBX1 was found to be upregulated in most cancer forms, with heightened expression correlating with adverse patient prognoses. Within the context of HCC, elevated levels of CBX1 were consistently indicative of poorer clinical outcomes. Suppression of CBX1 through knockdown methodologies markedly diminished HCC cell proliferation, invasive capabilities, migratory activity, Epithelial−mesenchymal transition (EMT) processes, and resistance to Tyrosine kinase inhibitors (TKIs) . Contrastingly, CBX1 augmentation facilitated the opposite effects. Subsequent investigative efforts revealed CBX1 to be a promoter of EMT and a contributor to increased TKI resistance within HCC cells, mediated via the IGF-1R/AKT/ SNAIL signaling axis. The oncogenic activities of CBX1 proved to be attenuable either by AKT pathway inhibition or by targeted silencing of IGF-1R. Conclusions The broad overexpression of CBX1 in pan-cancer and specifically in HCC positions it as a putative oncogenic entity. It is implicated in forwarding HCC progression and exacerbating TKI resistance through its interaction with the IGF- 1R/AKT/SNAIL signaling cascade. Keywords Chromobox Homolog 1 · Hepatocellular carcinoma · TKI resistance · AKT signaling · Epithelial−mesenchymal transition Abbreviations CBX1 Chromobox Homolog 1 HCC Hepatocellular carcinoma RT-PCR Real-time polymerase chain reaction Su-Su Zheng, Jing-Fang Wu, Wei-Xun-Wu, Jin-Wu Hu authors contributed equally to this work, and should be considered as cofirst authors. Extended author information available on the last page of the article WB CCK-8 EMT ELISA TKIs ScRNA-seq TCGA GSEA BCLC TTR Western blotting Cell counting kit-8 Epithelial−mesenchymal transition Enzyme-linked immunosorbent Assay Tyrosine kinase inhibitors Single-cell RNA sequencing The cancer genome atlas Gene set enrichment analysis Barcelona clinic liver cancer Time to recurrence OS Overall survival PFS Progression-free survival TMAs Tissue microarrays BLCA Bladder urothelial carcinoma BRCA Breast invasive carcinoma CHOL Cholangiocarcinoma COAD Colon adenocarcinoma ESCA Esophageal carcinoma ELISA Enzyme-linked immunosorbent assay HNSC Head and nec

FAQs

What is the main purpose of studying CBX1 in hepatocellular carcinoma?

To determine whether CBX1 contributes to HCC progression and whether it explains resistance to sorafenib and lenvatinib, using the IGF-1R/AKT/SNAIL signaling pathway as a proposed mechanism.

How was CBX1 expression characterized in this study?

CBX1 expression profiles were assessed with bioinformatics and single-cell RNA sequencing, and in HCC it was measured in tissues using RT-PCR, Western blotting, and immunohistochemistry.

What functional effects does CBX1 have on HCC cells and drug response?

CBX1 knockdown reduces proliferation, invasion, migration, EMT, and resistance to tyrosine kinase inhibitors, while CBX1 overexpression produces opposite effects and promotes EMT-related TKI resistance through IGF-1R/AKT/SNAIL signaling.

Sep 21, 2026

Upload by Riley