Journal article
PACT promotes the metastasis of basal-like breast cancer through Rac1 SUMOylation and activation
Oncogene, Vol.41(37), pp.4282-4294
09/01/2022
DOI: 10.1038/s41388-022-02431-6
Abstract
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.
Details
- Title: Subtitle
- PACT promotes the metastasis of basal-like breast cancer through Rac1 SUMOylation and activation
- Creators
- Luyao Wei - Shanghai University of Traditional Chinese MedicineWantao WangJunxia YaoZhengyu CuiZihang XuHanqing DingXiaojun WuDeheng WangJia LuoZun-Ji Ke
- Resource Type
- Journal article
- Publication Details
- Oncogene, Vol.41(37), pp.4282-4294
- DOI
- 10.1038/s41388-022-02431-6
- ISSN
- 0950-9232
- eISSN
- 1476-5594
- Grant note
- DOI: 10.13039/501100001809, name: National Natural Science Foundation of China, award: 31570921, 31701217; DOI: 10.13039/501100010032, name: Foundation of Shanghai Municipal Commission of Health and Family Planning, award: 201540206
- Language
- English
- Date published
- 09/01/2022
- Academic Unit
- Pathology
- Record Identifier
- 9984296997802771
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