Molecular Signaling & Drug Discovery Laboratory, Department of Biochemistry, Central University of Punjab, Bathinda 151401, India.
Department of Urology, Case Western Reserve University, Cleveland, OH 44106, USA.
Int J Mol Sci. 2022 Sep 12;23(18):10577. doi: 10.3390/ijms231810577.
Signal peptide, CUB, and EGF-like domain-containing proteins (SCUBE) are secretory cell surface glycoproteins that play key roles in the developmental process. SCUBE proteins participate in the progression of several diseases, including cancer, and are recognized for their oncogenic and tumor suppressor functions depending on the cellular context. SCUBE proteins promote cancer cell proliferation, angiogenesis, invasion, or metastasis, stemness or self-renewal, and drug resistance. The association of SCUBE with other proteins alters the expression of signaling pathways, including Hedgehog, Notch, TGF-β/Smad2/3, and β-catenin. Further, SCUBE proteins function as potential prognostic and diagnostic biomarkers for breast cancer, renal cell carcinoma, endometrial carcinoma, and nasopharyngeal carcinoma. This review presents key features of SCUBE family members, and their structure and functions, and highlights their contribution in the development and progression of cancer. A comprehensive understanding of the role of SCUBE family members offers novel strategies for cancer therapy.
信号肽、CUB 和表皮生长因子样结构域蛋白（SCUBE）是分泌型细胞表面糖蛋白，在发育过程中发挥关键作用。SCUBE 蛋白参与多种疾病的进展，包括癌症，并因其在细胞环境中的致癌和肿瘤抑制功能而受到认可。SCUBE 蛋白促进癌细胞增殖、血管生成、侵袭或转移、干性或自我更新以及耐药性。SCUBE 与其他蛋白质的结合改变了信号通路的表达，包括 Hedgehog、Notch、TGF-β/Smad2/3 和 β-连环蛋白。此外，SCUBE 蛋白可作为乳腺癌、肾细胞癌、子宫内膜癌和鼻咽癌的潜在预后和诊断生物标志物。本综述介绍了 SCUBE 家族成员的主要特征及其结构和功能，并强调了它们在癌症发生和发展中的作用。全面了解 SCUBE 家族成员的作用为癌症治疗提供了新的策略。
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