Nature Communications · 2019 · 58 citations · 47 references
MedicineMolecular GeneticsOncologyMetastasisMolecular OncologyTumor ProgressionCancer Cell SignalingColorectal CancerMalignant NeoplasmsMetastatic Signaling PathwaysOncogenic Signaling PathwaysTumor Suppressor GenesCancer Signaling PathwaysMicrorna Function In CancerMicrorna In CancerTherapeutic Target IdentificationTranscriptional UpregulationTumor Suppressor Gene DeletionsTumor Suppressor Gene LossTumor Suppressor Loss
Wilms tumor gene on the X chromosome (WTX) is a putative tumor suppressor gene in Wilms tumor, but its expression and functions in other tumors are unclear. Colorectal cancer (CRC) is the third leading cause of cancer-related deaths in women and the second leading cause in men in the United States. We demonstrated that WTX frequently lost in CRC which was highly correlated with cell proliferation, tumor invasion and metastasis. Mechanistically, WTX loss disrupts the interaction between RhoGDIα and CDC42 by losing of the binding with RhoGDIα and triggers the activation of CDC42 and its downstream cascades, which promotes CRC development and liver metastasis. The aberrant upregulation of miR-20a/miR-106a were identified as the reason of WTX loss in CRC both in vivo and in vitro. These study defined the mechanism how miR-20a/miR-106a-mediated WTX loss regulates CRC progression and metastasis, and provided a potential therapeutic target for preventing CRC progression.
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Wilms Tumor Suppressor WTX Negatively Regulates WNT/ß-Catenin Signaling
Michael B. Major, Nathan D. Camp, Jason D. Berndt et al. · Science · 2007 · 413 citations
An X Chromosome Gene, <i>WTX</i> , Is Commonly Inactivated in Wilms Tumor
Miguel N. Rivera, Woo‐Jae Kim, Julie Wells et al. · Science · 2007 · 345 citations