Cellular signalling · 2025
COL1A1 promotes clear cell renal cell carcinoma progression through the Wnt/β-catenin signaling pathway.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Ji Xing, Yun Yongyang, Zhu Zhenpeng, Wu Tianyu, Ruan Mingjian, Fan Yu, Zhang Qian
Аннотация
OBJECTIVE: To investigate COL1A1 expression, prognostic significance, functional roles, and underlying mechanisms in clear cell renal cell carcinoma (ccRCC).
METHODS: COL1A1 expression was analyzed using public databases, Western blotting, and immunohistochemistry (IHC). Functional effects were evaluated through both loss-of-function and gain-of-function assays in vitro. An in vivo xenograft model was used to assess tumor growth and confirm epithelial-mesenchymal transition (EMT) marker changes by IHC. Mechanistic investigations involved dual-rescue experiments with a Wnt/β-catenin activator and inhibitor, and functional location assays using a secretion inhibitor and recombinant protein.
RESULTS: COL1A1 was significantly upregulated in ccRCC, and high expression independently predicted poor prognosis. Bidirectional perturbations supported an oncogenic role: knockdown inhibited, whereas overexpression enhanced, cell proliferation, migration, invasion, and EMT. In vivo, COL1A1 knockdown suppressed tumor growth and histologically reversed EMT. Mechanistically, functional location studies demonstrated that COL1A1 acts predominantly from the extracellular space to activate Wnt/β-catenin signaling. This dependency was corroborated by dual-rescue experiments, in which pathway activation restored the knockdown phenotype, whereas β-catenin inhibition abrogated the effects of COL1A1 overexpression.
CONCLUSION: COL1A1 is a key oncogene in ccRCC, promoting progression by activating the Wnt/β-catenin axis. COL1A1 holds potential as a prognostic biomarker and therapeutic target for ccRCC.
METHODS: COL1A1 expression was analyzed using public databases, Western blotting, and immunohistochemistry (IHC). Functional effects were evaluated through both loss-of-function and gain-of-function assays in vitro. An in vivo xenograft model was used to assess tumor growth and confirm epithelial-mesenchymal transition (EMT) marker changes by IHC. Mechanistic investigations involved dual-rescue experiments with a Wnt/β-catenin activator and inhibitor, and functional location assays using a secretion inhibitor and recombinant protein.
RESULTS: COL1A1 was significantly upregulated in ccRCC, and high expression independently predicted poor prognosis. Bidirectional perturbations supported an oncogenic role: knockdown inhibited, whereas overexpression enhanced, cell proliferation, migration, invasion, and EMT. In vivo, COL1A1 knockdown suppressed tumor growth and histologically reversed EMT. Mechanistically, functional location studies demonstrated that COL1A1 acts predominantly from the extracellular space to activate Wnt/β-catenin signaling. This dependency was corroborated by dual-rescue experiments, in which pathway activation restored the knockdown phenotype, whereas β-catenin inhibition abrogated the effects of COL1A1 overexpression.
CONCLUSION: COL1A1 is a key oncogene in ccRCC, promoting progression by activating the Wnt/β-catenin axis. COL1A1 holds potential as a prognostic biomarker and therapeutic target for ccRCC.