TRIM59 deficiency curtails breast cancer metastasis through SQSTM1-selective autophagic degradation of PDCD10.
Summary of "TRIM59 deficiency curtails breast cancer metastasis through SQSTM1-selective autophagic degradation of PDCD10."
Receptor-driven selective macroautophagy/autophagy delivers ubiquitinated targets for autophagosomal clearance to maintain metabolic homeostasis and orchestrate reparative inflammatory responses. Deregulated autophagy is linked to tumor progression, but the exact mechanisms of selective autophagy in the spatiotemporal control of cell polarity signaling components during cancer metastasis remain ill-defined. Our recent study has demonstrated that TRIM59, an E3 ligase upregulated in metastatic breast cancer, is required for cancer cell survival and metastasis. Genetic depletion of TRIM59 suppresses cancer metastasis by promoting RNFT1-induced K63 polyubiquitination and SQSTM1-directed autophagic degradation of PDCD10, thereby boosting ROCK (Rho associated coiled-coil containing protein kinase)-induced actomyosin contractility and enhancing CDH1-mediated adhesion formation.
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Journal Details
This article was published in the following journal.
Name: Autophagy
ISSN: 1554-8635
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/30653426
- DOI: http://dx.doi.org/10.1080/15548627.2019.1569951
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Medical and Biotech [MESH] Definitions
Inflammatory Breast Neoplasms
Metastatic breast cancer characterized by EDEMA and ERYTHEMA of the affected breast due to LYMPHATIC METASTASIS and eventual obstruction of LYMPHATIC VESSELS by the cancer cells.
Carcinoma, Lobular
A infiltrating (invasive) breast cancer, relatively uncommon, accounting for only 5%-10% of breast tumors in most series. It is often an area of ill-defined thickening in the breast, in contrast to the dominant lump characteristic of ductal carcinoma. It is typically composed of small cells in a linear arrangement with a tendency to grow around ducts and lobules. There is likelihood of axillary nodal involvement with metastasis to meningeal and serosal surfaces. (DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, p1205)
Breast Cancer Lymphedema
Abnormal accumulation of lymph in the arm, shoulder and breast area associated with surgical or radiation breast cancer treatments (e.g., MASTECTOMY).
Capecitabine
A deoxycytidine derivative and fluorouracil PRODRUG that is used as an ANTINEOPLASTIC ANTIMETABOLITE in the treatment of COLON CANCER; BREAST CANCER and GASTRIC CANCER.
Mucin-1
Carbohydrate antigen elevated in patients with tumors of the breast, ovary, lung, and prostate as well as other disorders. The mucin is expressed normally by most glandular epithelia but shows particularly increased expression in the breast at lactation and in malignancy. It is thus an established serum marker for breast cancer.
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