Update on the effects of the sodium pump α1 subunit on human glioblastoma: from the laboratory to the clinic

ABSTRACT

Introduction: Glioblastoma is a debilitating disease that is associated with poor prognosis and a very limited response to therapies; thus, molecularly targeted therapeutics and personalized therapy are urgently needed. The Na⁺/K⁺-ATPase sodium pump is a transmembrane protein complex that has recently been recognized as an important transducer and integrator of various signals. The sodium pump α1 subunit, which is highly expressed in most glioblastomas compared with that in normal brain tissues, is an emerging cancer target that merits further investigation.

Area covered: The purpose of this narrative review is to explore the important roles of the sodium pump α1 subunit in glioblastoma and analyze its potential therapeutic applications.

Expert opinion: Expression of the sodium pump α1 subunit in glioblastoma tissues is generally higher than that in normal tissues. Sodium pump α1 subunit-mediated pivotal antiglioblastoma signaling pathways have been reviewed, and their impact on the sensitivity of glioblastoma cells to anticancer drugs has recently been clarified. In addition, various pharmacologically optimized sodium pump inhibitors have recently reached early clinical trials, and explorations of sodium pump α1 subunit inhibitors may hold promise for the development of stratification strategies in which patients are treated based on their isoform expression status.

KEYWORDS:

• Cardiotonic steroids
• glioblastoma
• sodium pump
• target
• therapy

Article highlights

• The sodium pump α1 subunit potentially mediates various antiglioblastoma signaling pathways.

• The sodium pump α1 subunit potentially affects the sensitivity of glioblastoma cells to drugs.

• Sodium pump α1 subunit inhibitors might be promising for glioblastoma treatment.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This work is supported by grants from National Natural Science Foundation of China (Nos. 81372714, 81672480), Liaoning Provincial Natural Science Foundation of China (No. 201602244), Distinguished Professor Project of Liaoning Province, Special Grant for Translational Medicine, Dalian Medical University (No. 2015002). Basic research projects in colleges and universities of Liaoning Province (No. LQ2017033).