The HACE1 E3 ligase mediates RAC1-dependent control of mTOR signaling complexes.

HACE1 is a HECT family E3 ubiquitin-protein ligase with broad but incompletely understood tumor suppressor activity. Here, we report a previously unrecognized link between HACE1 and signaling complexes containing mammalian target of rapamycin (mTOR). HACE1 blocks mTORC1 and mTORC2 activities by reducing mTOR stability in an E3 ligase-dependent manner.

A MYCN-independent mechanism mediating secretome reprogramming and metastasis in -amplified neuroblastoma.

amplification () is a defining feature of high-risk neuroblastoma (NB) and predicts poor prognosis. However, whether genes within or in close proximity to the amplicon also contribute to NB remains poorly understood. Here, we identify that , a transcription factor encoding gene neighboring the locus, is frequently coexpressed with and promotes cell survival in NB.

HACE1 blocks HIF1α accumulation under hypoxia in a RAC1 dependent manner.

Uncovering the mechanisms that underpin how tumor cells adapt to microenvironmental stress is essential to better understand cancer progression. The HACE1 (HECT domain and ankyrin repeat-containing E3 ubiquitin-protein ligase) gene is a tumor suppressor that inhibits the growth, invasive capacity, and metastasis of cancer cells. However, the direct regulatory pathways whereby HACE1 confers this tumor-suppressive effect remain to be fully elucidated.

Development of Whole-Proteome Arrays and Identification of Serologic Biomarkers for Noncardia Gastric Cancer in the MCC-Spain Study.

Background: () is a bacterial carcinogen and the leading risk factor for noncardia gastric cancer (NCGC). Detecting antibodies against specific proteins in peripheral blood can be applied to characterize infection and determine disease associations. Most studies analyzing the association between infection and gastric cancer have focused on previously identified antigens, predominantly the virulence factor cytotoxin-associated gene A (CagA).

HACE1 is a potential tumor suppressor in osteosarcoma.

Osteosarcoma is a malignant bone sarcoma characterized by extensive genomic disruption and a propensity for metastatic spread. Osteoid production suggests a close relationship with normal osteoblasts, and the latter are the presumptive cell of origin of this disease. The HACE1 gene, localized to human chromosome 6q21, encodes the HACE1 HECT E3 ligase, a tumor suppressor in diverse tumors that acts in part by targeting the activated form of RAC1 GTPase for proteasomal degradation.