Sgce-flox Mouse

Sgce, also known as ε-Sarcoglycan, is a type Ⅰ single-transmembrane protein. In breast cancer, it has been implicated in promoting cancer stemness. It promotes the transcription of FGF-BP1 by interacting with the Sp1 transcription factor, and the secreted FGF-BP1 activates FGF-FGFR signaling to enhance cancer cell stemness. It also functions as a sponge molecule to inhibit the lysosomal degradation of EGFR, thus stabilizing the EGFR protein and promoting breast cancer stem cell self-renewal, chemoresistance, and metastasis [2,5].

Mutations in Sgce are the most frequent known genetic cause of myoclonus-dystonia (M-D), a pleiotropic neuropsychiatric disorder. Japanese patients with M-D were found to have various loss-of-function mutations in Sgce, including nonsense, frameshift, missense, in-frame deletion, and splice donor site mutations [4]. Myoclonus-dystonia may be underdiagnosed due to pleiotropy, mild phenotypes, variable penetrance, and impaired access to genetic testing. Deleterious Sgce variants are relatively prevalent in the population, with an estimated 1/348 individuals in the US population harboring a variant with a certain CADD score [3]. Children with Sgce-myoclonus-dystonia show recognizable dystonic patterns such as writer's cramp and specific gait dystonia patterns, and use sensory tricks, which may aid in early diagnosis [1]. Some patients with Sgce-related M-D also have seizures, and altered neuronal excitability has been implicated in its pathogenesis [6].

In conclusion, Sgce has important functions in breast cancer stemness regulation and is closely associated with myoclonus-dystonia. Studies on Sgce, especially those involving loss-of-function mutations in patients, have enhanced our understanding of the biological processes underlying these disease conditions, potentially guiding the development of new diagnostic and therapeutic strategies for breast cancer and myoclonus-dystonia.