HERC1 Regulates Breast Cancer Cells Migration and Invasion

Abstract

Tumor cell migration and invasion into adjacent tissues is one of the hallmarks of cancer and the first step towards secondary tumors formation, which represents the leading cause of cancer-related deaths. This process is considered an unmet clinical need in the treatment of this disease, particularly in breast cancers characterized by high aggressiveness and metastatic potential. To identify and characterize genes with novel functions as regulators of tumor cell migration and invasion, we performed a genetic loss-of-function screen using a shRNA library directed against the Ubiquitin Proteasome System (UPS) in a highly invasive breast cancer derived cell line. Among the candidates, we validated HERC1 as a gene regulating cell migration and invasion. Furthermore, using animal models, our results indicate that HERC1 silencing affects primary tumor growth and lung colonization. Finally, we conducted an in silico analysis using publicly available protein expression data and observed an inverse correlation between HERC1 expression levels and breast cancer patients’ overall survival. Altogether, our findings demonstrate that HERC1 might represent a novel therapeutic target for the development or improvement of breast cancer treatment.

Construction of circRNA-miRNA-mRNA network and identification of novel potential biomarkers for non-small cell lung cancer

“…It may relate to the inter-heterogeneity in different studies and samples. Similar to this research, Rossi et al have also revealed that HERC1 can regulate cell migration and invasion, and has an inverse correlation with breast cancer patients OS [ 47 ]. In short, the mRNAs in circRNA‐related ceRNA networks may have key roles in the progression of NSCLC patients.…”

HERC3 regulates epithelial-mesenchymal transition by directly ubiquitination degradation EIF5A2 and inhibits metastasis of colorectal cancer

“…HERC E3s are previously reported to have pivotal roles in many cancers. For instance, HERC1 was indicated to modulate the migration and invasion in breast cancer cells [19]. HERC2 was Fig.…”

“…reported to have an important function in the p53-MDM2 axis and might provide novel insight in cancers [20]. HERC4 interacts with miRNA and induces breast cancer progression via inhibiting LATS1 [19]. HERC5 is identified to be a potential prognostic biomarker for breast cancer via bioinformatics analysis [21].…”

“…Many components of the HERC E3s are reported to be crucial in various cancers. HERC1 can modulate breast cancer cells migration and invasion [19]. HERC2 exerts a pivotal function in the p53-MDM2 axis [20].…”

“…HERC2 exerts a pivotal function in the p53-MDM2 axis [20]. HERC4 is indicated to promote breast cancer progression via inhibiting tumor suppressor LATS1 via interaction with miRNA [19]. HERC5 is revealed to be a prognostic biomarker for breast cancer through bioinformatic analysis [21].…”