4.5 Article

UCHL1 promotes cancer stemness in triple-negative breast cancer

Journal

PATHOLOGY RESEARCH AND PRACTICE
Volume 240, Issue -, Pages -

Publisher

ELSEVIER GMBH
DOI: 10.1016/j.prp.2022.154235

Keywords

UCHL1; Cancer stemness; Triple -negative breast cancer; EMT; Prognosis

Categories

Funding

  1. Joint Construction Project of Henan Medical Science and Technology Research Plan
  2. National Natural Science Foundation of China
  3. China Postdoctoral Science Foundation
  4. Key Research and Development Projects of Shaanxi Province
  5. [LHGJ20191432]
  6. [82103522]
  7. [2021TQ0362]
  8. [2022SF- 029]

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The study found that UCHL1 was overexpressed in TNBC tissues and was associated with poor prognosis. UCHL1 promoted cancer stemness and enhanced the migration and invasion ability of TNBC cells. These findings suggest that UCHL1 may play a crucial role in the malignant progression of TNBC and could be a potential therapeutic target for TNBC patients.
Background: Triple-negative breast cancer (TNBC) is a special kind of breast cancer with strong ability of invasion and metastasis. UCHL1 belongs to the ubiquitin carboxy-terminal hydrolase family and is found to be increased in a variety of malignancies, but its expression in TNBC is unknown.Methods: First, we analyzed the expression of UCHL1 in 128 TNBC specimens and paired adjacent normal tissues from 17 TNBC patients undergoing curative resection by immunohistochemistry. Then, the relationship between UCHL1 and cancer stemness was investigated by cell flow cytometry, spheroid formation assays and western blot. Moreover, cell scratch assay and Transwell assays were performed to explore whether UCHL1 promotes the migration and invasion of TNBC cells. Finally, we constructed a xenografts model of TNBC cell lines to observe the effect of UCHL1 on tumorigenesis in vivo.Results: UCHL1 was overexpressed in TNBC tissues and associated with poor prognosis. UCHL1 promoted stem cancer cells properties, including the percentage of CD44+/CD24- cells, sphere-forming ability and CSCs related markers. Furthermore, Scratch assay and Transwell assay proved that UCHL1 enhanced the migration and in-vasion of TNBC cells. The experimental results of xenografts model in nude mice showed that UCHL1 promoted tumorigenesis of TNBC in vivo.Conclusion: UCHL1 may play a role in the malignant progression of TNBC by maintaining the stemness and promoting cell invasion and is expected to become a potential therapeutic target for TNBC patients.

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