TSSC4 Human

TSSC4 has been identified as a novel tumor suppressor and autophagy inhibitor. Autophagy is a cellular process involving the degradation and recycling of cellular components, which can play a dual role in cancer by either promoting cell survival or inducing cell death . In the context of glioblastoma (GBM), the most aggressive type of brain cancer in adults, TSSC4 has shown significant potential in inhibiting cancer cell growth .

TSSC4 interacts with the autophagy protein LC3, inhibiting autophagy-induced cell death (AuICD) in cancer cells . This interaction is crucial for its tumor-suppressing function. Overexpression of TSSC4 has been shown to prevent cell death induced by temozolomide (TMZ), a standard chemotherapy drug used in GBM treatment . When TSSC4 is mutated in its conserved LC3-interacting region, it loses its ability to inhibit autophagy and prevent cell death .

Recent studies have demonstrated that TSSC4 expression is upregulated by the activation of the epidermal growth factor receptor (EGFR) in GBM cells . EGFR variant III (EGFRvIII) is the most common mutation in GBM, and its expression leads to increased levels of TSSC4, which in turn decreases TMZ-induced cell death . Knockout of TSSC4 in EGFRvIII-expressing GBM cells results in increased autophagy and cell death, suggesting that TSSC4 downregulation promotes TMZ-induced AuICD .

Given its role in inhibiting autophagy and promoting cell survival, TSSC4 represents a promising target for sensitizing GBM cells to TMZ treatment . By targeting TSSC4, it may be possible to enhance the effectiveness of chemotherapy and improve outcomes for patients with GBM.