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SHCBP1 通过 TGFβ 通路促进食管鳞癌的进展。

SHCBP1 Promotes the Progression of Esophageal Squamous Cell Carcinoma Via the TGFβ Pathway.

机构信息

International Medical Service Center.

Breast Surgical Ward, Shandong Cancer Hospital, Jinan City.

出版信息

Appl Immunohistochem Mol Morphol. 2021 Feb 1;29(2):136-143. doi: 10.1097/PAI.0000000000000858.

Abstract

Esophageal cancer (EC) is known as a type of common malignant tumor, with the incidence ranking eighth worldwide. Because of the high metastasis of advanced EC, the total survival rate has been quite low. Esophageal squamous cell carcinoma (ESCC) is a main type of EC. Targeted therapy for ESCC has become a new direction; however, newly therapeutic targets are also badly needed. Shc SH2 domain-binding protein (SHCBP1) is located on 16q11.2, which is a downstream protein of the Shc adaptor. SHCBP1 participates in the regulation of several physiological and pathologic processes, such as cytokinesis. Recent studies have found that SHCBP1 was abnormally upregulated in multiple types of tumors, such as breast cancer and liver cancer, and that it affects the proliferation and motility of cancer cells in vitro. However, it remains unclear whether SHCBP1 is related to the progression of EC. Herein, we found the upregulation of SHCBP1 in human EC tissues. Our findings further demonstrated that SHCBP1 expression was related to the clinical features of ESCC patients. We found that SHCBP1 depletion inhibited the proliferation and motility of ESCC cells via the transforming growth factor β pathway and that it suppressed the growth of tumors in mice. We, therefore, concluded that SHCBP1 could serve as a promising EC molecular target.

摘要

食管癌(EC)是一种常见的恶性肿瘤,其发病率在全球范围内排名第八。由于晚期 EC 转移率高,总生存率一直相当低。食管鳞状细胞癌(ESCC)是 EC 的主要类型。ESCC 的靶向治疗已成为新的方向;然而,也急需新的治疗靶点。衔接蛋白 Shc SH2 结构域结合蛋白(SHCBP1)位于 16q11.2,是 Shc 衔接蛋白的下游蛋白。SHCBP1 参与调节细胞分裂等几种生理和病理过程。最近的研究发现,SHCBP1 在多种类型的肿瘤中异常上调,如乳腺癌和肝癌,并且它影响体外癌细胞的增殖和迁移。然而,SHCBP1 是否与 EC 的进展有关仍不清楚。在此,我们发现 SHCBP1 在人 EC 组织中上调。我们的研究结果进一步表明,SHCBP1 表达与 ESCC 患者的临床特征有关。我们发现 SHCBP1 耗竭通过转化生长因子β通路抑制 ESCC 细胞的增殖和迁移,并抑制小鼠肿瘤的生长。因此,我们得出结论,SHCBP1 可以作为一个有前途的 EC 分子靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e55/7993916/7d221d7b27ed/pai-29-136-g001.jpg

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