期刊
ONCOGENE
卷 41, 期 37, 页码 4282-4294出版社
SPRINGERNATURE
DOI: 10.1038/s41388-022-02431-6
关键词
-
资金
- National Natural Science Foundation of China [31701217, 31570921]
- Shanghai Key Laboratory of Health Identification and Assessment [13DZ2261000]
- Shanghai Municipal Commission of Health and Family Planning [201540206]
This study identifies protein activator of the interferon-induced protein kinase (PACT) as a key player in basal-like breast cancer (BLBC) metastasis. High expression of PACT is associated with poor prognosis in BLBC patients. It is found that PACT regulates BLBC metastasis by interacting with SUMO-conjugating enzyme Ubc9.
Most basal-like breast cancers (BLBCs) are triple-negative breast cancers (TNBCs), which is associated with high malignancy, high rate of recurrence and distant metastasis, and poor prognosis among all types of breast cancer. However, there are currently no effective therapies for BLBC. Furthermore, chemoresistance limits the therapeutic options for BLBC treatment. In this study, we screen out protein activator of the interferon-induced protein kinase (PACT) as an essential gene in BLBC metastasis. We find that high PACT expression level was associated with poor prognosis among BLBC patients. In vivo and in vitro investigations indicated that PACT could regulate BLBC metastasis by interacting with SUMO-conjugating enzyme Ubc9 to stimulate the SUMOylation and thus consequently the activation of Rac1. BLBC patients receiving chemotherapy presents poorer prognosis with PACT high expression, and PACT disruption sensitizes experimental mammary tumor metastases to chemotherapy, thus providing insights to consider PACT as a potential therapeutic target to overcome acquired chemoresistance in BLBC.
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