Department of Thoracic Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.
Environ Toxicol. 2024 Jan;39(1):9-22. doi: 10.1002/tox.23938. Epub 2023 Aug 16.
Aberrant expression of MUC1 correlates with the progression of esophageal squamous cell carcinoma (ESCC), this study aimed to explore the effect of targeting MUC1 by Go-203 on malignant behavior of ESCC and the underlying mechanism.
IHC was used to examine the expression of MUC1 and DNAJB6 in ESCC samples. qRT-PCR and western blotting were used to examine the expression of MUC1 and DNAJB6 in ESCC cell lines. CCK8, wound healing, and transwell assays were used to determine the effect of regulating MUC1/DNAJB6 on the proliferation, migration, and invasion of ESCC cells. The effect of overexpressing/targeting MUC1 on the activation of the AKT/HSF-1 pathway was determined by western blotting. A negative correlation was confirmed between the expression of DNAJB6 and MUC1 in ESCC tissue samples by IHC, and high expression of MUC1 and low expression of DNAJB6 correlated with lymph node metastasis in ESCC patients. Overexpressing MUC1 downregulated the expression of DNAJB6, promoted ESCC proliferation, invasion, migration and activated the AKT pathway, while targeting MUC1 suppressed proliferation, invasion, migration, and the AKT pathway and up-regulated DNAJB6 expression in vitro. Moreover, MUC1 increased the phosphorylation of HSF-1 via the AKT pathway, and inhibiting AKT-HSF-1 increased the expression of DNAJB6 in vitro.
This study indicated that MUC1 could promote tumorigenesis and metastasis in ESCC by downregulating DNAJB6 expression through AKT-HSF-1 pathway.
MUC1 的异常表达与食管鳞状细胞癌（ESCC）的进展相关，本研究旨在探讨靶向 MUC1 的 Go-203 对 ESCC 恶性行为的影响及其潜在机制。
免疫组化（IHC）用于检测 ESCC 样本中 MUC1 和 DNAJB6 的表达。qRT-PCR 和 Western blot 用于检测 ESCC 细胞系中 MUC1 和 DNAJB6 的表达。CCK8、划痕愈合和 Transwell 测定用于确定调节 MUC1/DNAJB6 对 ESCC 细胞增殖、迁移和侵袭的影响。Western blot 用于确定过表达/靶向 MUC1 对 AKT/HSF-1 通路激活的影响。通过 IHC 证实了 DNAJB6 与 ESCC 组织样本中 MUC1 的表达之间存在负相关，并且 MUC1 高表达和 DNAJB6 低表达与 ESCC 患者的淋巴结转移相关。过表达 MUC1 下调了 DNAJB6 的表达，促进了 ESCC 的增殖、侵袭、迁移并激活了 AKT 通路，而靶向 MUC1 则抑制了体外增殖、侵袭、迁移和 AKT 通路，并上调了 DNAJB6 的表达。此外，MUC1 通过 AKT 通路增加了 HSF-1 的磷酸化，抑制 AKT-HSF-1 增加了体外 DNAJB6 的表达。
本研究表明，MUC1 通过 AKT-HSF-1 通路下调 DNAJB6 的表达，从而促进 ESCC 的肿瘤发生和转移。
