Metallothionein-3: Potential therapeutic target for sorafenib resistance in hepatocellular carcinoma

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62156489%3A43210%2F21%3A43920143" target="_blank" >RIV/62156489:43210/21:43920143 - isvavai.cz</a>

Alternative codes found

RIV/00216305:26620/21:PU142138

Result on the web

<a href="https://doi.org/10.1016/j.annonc.2021.05.660" target="_blank" >https://doi.org/10.1016/j.annonc.2021.05.660</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.annonc.2021.05.660" target="_blank" >10.1016/j.annonc.2021.05.660</a>

Result language

angličtina

Original language name

Metallothionein-3: Potential therapeutic target for sorafenib resistance in hepatocellular carcinoma

Original language description

Background: Metallothionein-3 (M-3) has poorly characterized functions in hepatocellular carcinoma (HCC). HCC is a significant health problem. Globally is the second most common cause of cancer-associated death. Sorafenib was originally identified as an inhibitor of multiple oncogenic kinases and remains the only approved systemic therapy for advanced HCC. However, acquired resistance to sorafenib has been found in HCC patients, which results in poor prognosis. Overexpression of MT-3 decreased the sensitivity of HCC cells to sorefenib. Here, we investigated the impact of MT-3 up-regulation in HCC cells and the mechanisms underlying the sorafenib-resistance. Methods: To increase the expression of MT-3 HCC cells were transiently transfected with a plasmid containing MT-3 gene or with empty vector. The cDNA microarrays were accomplished using the ElectraSenseTM Reader. MS analysis was performed using a Q-Exactive MS. We used chick chorioallantoic membrane assay as in vivo model. Results: A cDNA profiling revealed that sorafenib resistance has a specific transcriptomic signature involving genes responsible for ion transport, trafficking and DNA repair. Also, The MS analysis data strongly suggest that resistance HCC cells acquired a complex regulatory network that significantly affects the ability of HCC cells to remove the ROS and activation of glycolysis. We provide the first evidence that up-regulation of MT3 resulted in increased dissociation, invasion, and intravasation from the primary tumours to the veins. In addition, MT3 profoundly impacted blood migration of Nbl cells and their extravasation to chicken organs. Conclusion: From a perspective of future utilization of our data, we anticipate that several identified genes and proteins could serve as prognostic biomarkers of outcome of sorafenib therapy. The increased expression of MT-3 within tumour mass should inform about worse prognosis and also decreased efficiency of sorafenib-based chemotherapy in HCC.

Czech name

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Czech description

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Type

O - Miscellaneous

CEP classification

—

OECD FORD branch

10608 - Biochemistry and molecular biology

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2021

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů