Src同源和胶原同源结合蛋白1（SHCBP1）结合到SHC转化蛋白1（SHC1）的SH2结构域，并参与黏体组织和细胞质分裂的完成。已报道SHCBP1是促进癌症进展的癌驱动基因。然而，SHCBP1在调控肺腺癌（LUAD）细胞增殖和迁移方面的功能角色和潜在机制尚不完全了解。在这里，我们发现SHCBP1在LUAD组织中过度表达且与恶性预后有关。SHCBP1沉默抑制了LUAD细胞的增殖和迁移，通过阻断细胞周期并抑制上皮间质转化（EMT）来降低Cyclin-dependent kinase 1（CDK1）的表达。在机制上，CDK1的过表达逆转了SHCBP1沉默抑制的增殖和迁移，确定了CDK1作为SHCBP1的一个关键下游靶点。此外，我们提出了鲁卡帕尼可能是SHCBP1的一个小分子抑制剂，并通过体外和体内实验证实鲁卡帕尼通过抑制SHCBP1/CDK1通路来抑制LUAD细胞的增殖和迁移。我们的研究阐明了SHCBP1在促进LUAD细胞增殖和迁移中的新发现作用，并提示鲁卡帕尼作为LUAD治疗的潜在抑制剂。本文受版权保护。版权所有。

Src homolog and collagen homolog binding protein 1 (SHCBP1) binds to the SH2 domain of SHC-transforming protein 1 (SHC1) and is involved in midbody organization and cytokinesis completion. SHCBP1 has been reported to be a cancer driver gene, promoting cancer progression. However, the functional role and underlying mechanism of SHCBP1 in regulating lung adenocarcinoma (LUAD) cell proliferation and migration are incompletely understood. Here, we discovered that SHCBP1 is overexpressed in LUAD tissues and is associated with a poor prognosis. SHCBP1 knockdown inhibited LUAD cell proliferation and migration by arresting the cell cycle and preventing epithelial-mesenchymal transition (EMT) via decreasing cyclin-dependent kinase 1 (CDK1) expression. Mechanistically, CDK1 overexpression reversed SHCBP1 knockdown-induced inhibition of proliferation and migration, confirming CDK1 as a key downstream target of SHCBP1. In addition, we proposed that rucaparib may be a small-molecule inhibitor of SHCBP1 and validated both in vitro and in vivo that rucaparib inhibits cell proliferation and migration via suppression of the SHCBP1/CDK1 pathway in LUAD. Our study elucidates a newly identified role of SHCBP1 in promoting cell proliferation and migration in LUAD, and suggests rucaparib as a potential inhibitor for LUAD treatment.This article is protected by copyright. All rights reserved.