PRL-3 facilitates Hepatocellular Carcinoma progression by co-amplifying with and activating FAK

Zhou, Qiming; Zhou, Qianlei; Liu, Qinghua; He, Zhanghai; Yan, Yongcong; Lin, Jianhong; Chen, Zheng; He, Chuanchao; Mao, Kai; Wang, Jie; Zhou, Zhenyu; Xiao, Zhiyu; Zhang, Jianlong

doi:10.7150/thno.42069

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Nanotheranostics 2024; 8(3): 380-400. [Abstract] [Full text] [PDF]

Nanotheranostics 2024; 8(3): 344-379. [Abstract] [Full text] [PDF] [PubMed] [PMC]

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Theranostics 2020; 10(22):10345-10359. doi:10.7150/thno.42069 This issue Cite

Research Paper

PRL-3 facilitates Hepatocellular Carcinoma progression by co-amplifying with and activating FAK

Qiming Zhou^1,2,3*, Qianlei Zhou^1,2*, Qinghua Liu^1,2*, Zhanghai He⁴, Yongcong Yan^1,2, Jianhong Lin^1,2, Zheng Chen^1,2, Chuanchao He^1,2, Kai Mao^1,2, Jie Wang^1,2, Zhenyu Zhou^1,2✉, Zhiyu Xiao^1,2✉, Jianlong Zhang^1,2✉

1. Department of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China.
2. Guangdong Province Key laboratory of Malignant Tumour Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China.
3. Department of Thyroid Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China.
4. Department of Pathology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China.
*These authors share co-first authorship.

Citation:

Zhou Q, Zhou Q, Liu Q, He Z, Yan Y, Lin J, Chen Z, He C, Mao K, Wang J, Zhou Z, Xiao Z, Zhang J. PRL-3 facilitates Hepatocellular Carcinoma progression by co-amplifying with and activating FAK. Theranostics 2020; 10(22):10345-10359. doi:10.7150/thno.42069. https://www.thno.org/v10p10345.htm

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Abstract

Background: In addition to protein tyrosine kinases, accumulating evidence has shown that protein tyrosine phosphatases (PTPs) are suitable therapeutic targets in cancer. PRL-3 is a PTP member that has been well studied in many malignant tumours. The goal of the present study was to elucidate the role of PRL-3 in hepatocellular carcinoma (HCC), which remains largely unknown.

Methods: Bioinformatic and immunohistochemical analyses were performed to analyse PRL-3 expression in HCC tissue samples and determine its clinical relevance. PRL-3 gene copy number variations were evaluated by bioinformatic analysis and quantitative-genomic polymerase chain reaction. The biological functions of PRL-3 were investigated in vivo and vitro. Gene microarray assays, RT-qPCR, western blotting and luciferase experiments were performed to identify the downstream effectors of PRL-3 that mediate its functions in HCC.

Results: PRL-3 expression was upregulated in HCC samples from public databases and in cohort samples from our centre. High PRL-3 expression was associated with poor prognosis. Copy number gains and amplification of chromosome 8q24.3 in HCC were determined to be positively correlated with the PRL-3 overexpression. PRL-3 overexpression promoted HCC cell proliferation, migration and adhesion, while its loss had the opposite effects. Further study showed that focal adhesion kinase (FAK) was co-amplified and co-expressed with PRL-3 in HCC. Interestingly, PRL-3 also promoted the phosphorylation of FAK, which subsequently mediated the oncogenic functions of PRL-3 in HCC cells. Moreover, TGFB1 was identified as a downstream molecule of PRL-3. TGF-β signalling was shown to mediate the PRL-3-induced activation of FAK. Furthermore, the p38 and PI3K/AKT pathways were observed to mediate the PRL-3-induced expression of TGFB1 and the subsequent activation of FAK, while the activation of FAK in turn stimulated activation of the p38 and PI3K/AKT pathways, forming a PRL-3-triggered AKT/p38/TGFB1/FAK positive feedback loop.

Conclusion: Collectively, our findings indicate that the PTP PRL-3 plays a crucial role in the progression of HCC and provides an example of how co-amplified genes work together in HCC.

Keywords: HCC, PRL-3, Copy number variations, Phosphatase, TGFB1

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APA

Zhou, Q., Zhou, Q., Liu, Q., He, Z., Yan, Y., Lin, J., Chen, Z., He, C., Mao, K., Wang, J., Zhou, Z., Xiao, Z., Zhang, J. (2020). PRL-3 facilitates Hepatocellular Carcinoma progression by co-amplifying with and activating FAK. Theranostics, 10(22), 10345-10359. https://doi.org/10.7150/thno.42069.

ACS

Zhou, Q.; Zhou, Q.; Liu, Q.; He, Z.; Yan, Y.; Lin, J.; Chen, Z.; He, C.; Mao, K.; Wang, J.; Zhou, Z.; Xiao, Z.; Zhang, J. PRL-3 facilitates Hepatocellular Carcinoma progression by co-amplifying with and activating FAK. Theranostics 2020, 10 (22), 10345-10359. DOI: 10.7150/thno.42069.

NLM

CSE

Zhou Q, Zhou Q, Liu Q, He Z, Yan Y, Lin J, Chen Z, He C, Mao K, Wang J, Zhou Z, Xiao Z, Zhang J. 2020. PRL-3 facilitates Hepatocellular Carcinoma progression by co-amplifying with and activating FAK. Theranostics. 10(22):10345-10359.

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