最近的研究强调棕榈酰化（一种新型蛋白质翻译后修饰）是导致肿瘤发生和耐药性的各种信号通路中的关键角色。尽管如此，它在膀胱癌（BCa）发展中的作用仍然没有得到充分的了解。在这项研究中，ZDHHC9 作为 BCa 中显着上调的癌基因出现。在功能上，ZDHHC9敲低显着抑制肿瘤增殖，促进肿瘤细胞凋亡，并增强吉西他滨（GEM）和顺铂（CDDP）的疗效。从机制上讲，SP1 可转录激活 ZDHHC9 表达。 ZDHHC9 随后与 Bip 蛋白在半胱氨酸 420 (Cys420) 处结合并进行棕榈酰化，从而抑制未折叠蛋白反应 (UPR)。 Cys420 处的棕榈酰化增强了 Bip 的蛋白质稳定性并保留了其在内质网 (ER) 内的定位。 ZDHHC9 可能成为 BCa 的新治疗靶点，也可能有助于 GEM 和 CDDP 的联合治疗。版权所有 © 2024。由 Elsevier B.V. 出版。

Recent studies have highlighted palmitoylation, a novel protein post-translational modification, as a key player in various signaling pathways that contribute to tumorigenesis and drug resistance. Despite this, its role in bladder cancer (BCa) development remains inadequately understood. In this study, ZDHHC9 emerged as a significantly upregulated oncogene in BCa. Functionally, ZDHHC9 knockdown markedly inhibited tumor proliferation, promoted tumor cell apoptosis, and enhanced the efficacy of gemcitabine (GEM) and cisplatin (CDDP). Mechanistically, SP1 was found to transcriptionally activate ZDHHC9 expression. ZDHHC9 subsequently bound to and palmitoylated the Bip protein at cysteine 420 (Cys420), thereby inhibiting the unfolded protein response (UPR). This palmitoylation at Cys420 enhanced Bip's protein stability and preserved its localization within the endoplasmic reticulum (ER). ZDHHC9 might become a novel therapeutic target for BCa and could also contribute to combination therapy with GEM and CDDP.Copyright © 2024. Published by Elsevier B.V.