Targeting KK-LC-1 inhibits malignant biological behaviors of triple-negative breast cancer.
J Transl Med
; 21(1): 184, 2023 03 09.
Article
em En
| MEDLINE
| ID: mdl-36895039
ABSTRACT
BACKGROUND:
Cancer/testis antigens (CTAs) participate in the regulation of malignant biological behaviors in breast cancer. However, the function and mechanism of KK-LC-1, a member of the CTA family, in breast cancer are still unclear.METHODS:
Bioinformatic tools, immunohistochemistry, and western blotting were utilized to detect the expression of KK-LC-1 in breast cancer and to explore the prognostic effect of KK-LC-1 expression in breast cancer patients. Cell function assays, animal assays, and next-generation sequencing were utilized to explore the function and mechanism of KK-LC-1 in the malignant biological behaviors of triple-negative breast cancer. Small molecular compounds targeting KK-LC-1 were also screened and drug susceptibility testing was performed.RESULTS:
KK-LC-1 was significantly highly expressed in triple-negative breast cancer tissues than in normal breast tissues. KK-LC-1 high expression was related to poor survival outcomes in patients with breast cancer. In vitro studies suggested that KK-LC-1 silencing can inhibit triple-negative breast cancer cell proliferation, invasion, migration, and scratch healing ability, increase cell apoptosis ratio, and arrest the cell cycle in the G0-G1 phase. In vivo studies have suggested that KK-LC-1 silencing decreases tumor weight and volume in nude mice. Results showed that KK-CL-1 can regulate the malignant biological behaviors of triple-negative breast cancer via the MAL2/MUC1-C/PI3K/AKT/mTOR pathway. The small-molecule compound Z839878730 had excellent KK-LC-1 targeting ability and cancer cell killing ability. The EC50 value was 9.7 µM for MDA-MB-231 cells and 13.67 µM for MDA-MB-468 cells. Besides, Z839878730 has little tumor-killing effect on human normal mammary epithelial cells MCF10A and can inhibit the malignant biological behaviors of triple-negative breast cancer cells by MAL2/MUC1-C/PI3K/AKT/mTOR pathway.CONCLUSIONS:
Our findings suggest that KK-LC-1 may serve as a novel therapeutic target for triple-negative breast cancer. Z839878730, which targets KK-LC-1, presents a new path for breast cancer clinical treatment.Palavras-chave
Texto completo:
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Bases de dados:
MEDLINE
Assunto principal:
Neoplasias de Mama Triplo Negativas
/
Mycobacterium tuberculosis
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
J Transl Med
Ano de publicação:
2023
Tipo de documento:
Article