SASH1 is a prognostic indicator and potential therapeutic target in non-small cell lung cancer

Abstract

SASH1 (SAM and SH3 domain-containing protein 1) is a tumor suppressor protein that has roles in key cellular processes including apoptosis and cellular proliferation. As these cellular processes are frequently disrupted in human tumours and little is known about the role of SASH1 in the pathogenesis of the disease, we analysed the prognostic value of SASH1 in non-small cell lung cancers using publicly available datasets. Here, we show that low SASH1 mRNA expression is associated with poor survival in adenocarcinoma. Supporting this, modulation of SASH1 levels in a panel of lung cancer cell lines mediated changes in cellular proliferation and sensitivity to cisplatin. The treatment of lung cancer cells with chloropyramine, a compound that increases SASH1 protein concentrations, reduced cellular proliferation and increased sensitivity to cisplatin in a SASH1-dependent manner. In summary, compounds that increase SASH1 protein levels could represent a novel approach to treat NSCLC and warrant further study.

The emerging and diverse roles of the SLy/SASH1‐protein family in health and disease—Overview of three multifunctional proteins

“…87,120,122 Interestingly, Burgess et al recently demonstrated that increasing SASH1-protein levels by addition of chloropyramine is inhibiting the proliferation of lung cancer cells in a SASH1-dependent manner. 125 Moreover, this observation was accompanied by increased sensitivity of cancer cells toward cisplatin treatment. Therefore, the drug-mediated elevation of SASH1 concentrations should be considered as a potential future tool in anticancer therapy.…”

“…Interestingly, Burgess et al recently demonstrated that increasing SASH1‐protein levels by addition of chloropyramine is inhibiting the proliferation of lung cancer cells in a SASH1‐dependent manner 125 . Moreover, this observation was accompanied by increased sensitivity of cancer cells toward cisplatin treatment.…”

“…Moreover, this observation was accompanied by increased sensitivity of cancer cells toward cisplatin treatment. Therefore, the drug‐mediated elevation of SASH1 concentrations should be considered as a potential future tool in anticancer therapy 125 …”

“…Therefore, the drug-mediated elevation of SASH1 concentrations should be considered as a potential future tool in anticancer therapy. 125 In summary, SASH1 should be considered as a multitissue tumor suppressor with clinical relevance in a wide variety of cancerous diseases. SASH1 downregulation is associated with reduced patient survival and increased metastasis formation, probably due to its pro-apoptotic properties and its ability to inhibit EMT through interfering with the adapter protein CRKL.…”

CircRNA ITCH: Insight Into Its Role and Clinical Application Prospect in Tumor and Non-Tumor Diseases

“…In OS, circ-ITCH sponges miR-524 to up-regulate RASSF6, inducing OS cell death and limiting its proliferation, according to Zhou et al (Zhou W. et al, 2021). SAM and SH3 domain containing protein 1 (SASH1) is a tumor-suppressive protein that can regulate cell apoptosis and proliferation (Burgess et al, 2020). Circ-ITCH can suppress glioma growth and invasion by up-regulating SASH1 by targeting miR-106a-5p (Chen et al, 2021).…”