RHBDL2 promotes the proliferation, migration, and invasion of pancreatic cancer by stabilizing the N1ICD via the OTUD7B and activating the Notch signaling pathway.
RHBDL2 promotes the proliferation, migration, and invasion of pancreatic cancer by stabilizing the N1ICD via the OTUD7B and activating the Notch signaling pathway.
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RHBDL2通过OTUD7B稳定N1ICD并激活Notch信号通路促进胰腺癌的增殖、迁移和侵袭
DOI：
10.1038/s41419-022-05379-3
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发表时间：
2022-11-09
影响因子：
9
通讯作者：
Yu, Chao
中科院分区：
文献类型：
--
作者：
Chen, Shiyu;Cai, Kun;Zheng, Dijie;Liu, Yanqing;Li, Lin;He, Zhiwei;Sun, Chengyi;Yu, Chao
胰腺癌（PC）是最恶性的癌症类型之一，其特点是早期转移、对化疗药物反应有限、预后不良。因此，迫切需要探索新的PC治疗策略。人类菱形样 2 (RHBDL2) 在宫颈癌和乳腺癌中存在差异表达。然而，RHBDL2 与 PC 之间的相关性仍不清楚。我们发现RHBDL2在人类PC细胞和组织中高表达，并且与PC患者的远处转移和不良生存显着相关。功能获得和丧失分析表明，RHBDL2 可以在体外和体内加速 PC 细胞的增殖和迁移。 RNA-Seq结果提示RHBDL2可能参与Notch信号通路的激活。 IMR-1可以恢复RHBDL2介导的PC细胞的增殖和转移能力。 RHBDL2 与 Notch1 相互作用并裂解 Notch1，导致 N1ICD 的释放。 RHBDL2 降低了 N1ICD 的泛素化水平，并与含有卵巢肿瘤结构域的 7B (OTUD7B) 协同作用，通过泛素-蛋白酶体途径稳定 N1ICD。 RHBDL2 通过 OTUD7B 稳定 N1ICD 并激活 Notch 信号通路，从而促进 PC 细胞增殖和迁移。因此，针对这一新途径可能是 PC 的潜在治疗策略。
Pancreatic cancer (PC) is one of the most malignant types of cancer, and is characterized by early metastasis, limited response to chemotherapeutics, and poor prognosis. Therefore, there is an urgent need to explore new therapeutic strategies for PC treatment. Human rhomboid-like 2 (RHBDL2) is differentially expressed in cervical and breast cancer. However, the correlation between RHBDL2 and PC remains unclear. We found that RHBDL2 is highly expressed in human PC cells and tissues and is significantly associated with distant metastasis and poor survival of patients with PC. Gain- and loss-of-function assays indicated that RHBDL2 could accelerate PC cell proliferation and mobility in vitro and in vivo. The RNA-Seq results suggest that RHBDL2 may be involved in the activation of Notch signaling pathway. IMR-1 could restore the proliferation and metastatic capacity of PC cells mediated by RHBDL2. RHBDL2 interacted with and cleaved Notch1, resulting in the release of N1ICD. RHBDL2 decreased the ubiquitination level of N1ICD and collaborated with Ovarian tumor domain-containing 7B (OTUD7B) to stabilize N1ICD via the ubiquitin-proteasome pathway. RHBDL2 facilitated PC cell proliferation and mobility by stabilizing the N1ICD via the OTUD7B and activating the Notch signaling pathway. Thus, targeting this novel pathway may be a potential therapeutic strategy for PC.
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DOI：
10.1038/s41575-021-00457-x
发表时间：
2021-07
期刊：
Nature reviews. Gastroenterology & hepatology
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1002/advs.202004504
发表时间：
2021-08
期刊：
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
影响因子：
--
作者：
Gong Z;Li A;Ding J;Li Q;Zhang L;Li Y;Meng Z;Chen F;Huang J;Zhou D;Hu R;Ye J;Liu W;You H
通讯作者：
You H
影响因子：
4.8
作者：
Koch, Lydia;Kespohl, Birte;Garbers, Christoph
通讯作者：
Garbers, Christoph
OTUD7B稳定雌激素受体α并促进乳腺癌细胞的增殖。
影响因子：
9
作者：
Tang J;Wu Z;Tian Z;Chen W;Wu G
通讯作者：
Wu G
DOI：
10.1158/1078-0432.ccr-19-1373
发表时间：
2020-03-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Liu S;González-Prieto R;Zhang M;Geurink PP;Kooij R;Iyengar PV;van Dinther M;Bos E;Zhang X;Le Dévédec SE;van de Water B;Koning RI;Zhu HJ;Mesker WE;Vertegaal ACO;Ovaa H;Zhang L;Martens JWM;Ten Dijke P
通讯作者：
Ten Dijke P