TAZ facilitates breast tumor growth by promoting an immune-suppressive tumor microenvironment.

The core Hippo pathway module consists of a tumour-suppressive kinase cascade that inhibits the transcriptional coactivators Yes-associated protein (YAP) and WW domain-containing transcription regulator protein 1 (WWTR1; also known as TAZ). When the Hippo pathway is downregulated, as often occurs in breast cancer, YAP/TAZ activity is induced. To elaborate the roles of TAZ in triple-negative breast cancer (TNBC), we depleted Taz in murine TNBC 4T1 cells, using either CRISPR/Cas9 or small hairpin RNA (shRNA).

Different hotspot p53 mutants exert distinct phenotypes and predict outcome of colorectal cancer patients.

The TP53 gene is mutated in approximately 60% of all colorectal cancer (CRC) cases. Over 20% of all TP53-mutated CRC tumors carry missense mutations at position R175 or R273. Here we report that CRC tumors harboring R273 mutations are more prone to progress to metastatic disease, with decreased survival, than those with R175 mutations.

Cross-talk between mutant p53 and p62/SQSTM1 augments cancer cell migration by promoting the degradation of cell adhesion proteins.

Missense mutations in the p53 tumor suppressor abound in human cancer. Common (“hotspot”) mutations endow mutant p53 (mutp53) proteins with oncogenic gain of function (GOF), including enhanced cell migration and invasiveness, favoring cancer progression. GOF is usually attributed to transcriptional effects of mutp53.

LATS1 and LATS2 suppress breast cancer progression by maintaining cell identity and metabolic state.

Deregulated activity of LArge Tumor Suppressor (LATS) tumor suppressors has broad implications on cellular and tissue homeostasis. We examined the consequences of down-regulation of either LATS1 or LATS2 in breast cancer. Consistent with their proposed tumor suppressive roles, expression of both paralogs was significantly down-regulated in human breast cancer, and loss of either paralog accelerated mammary tumorigenesis in mice.

A Systematic p53 Mutation Library Links Differential Functional Impact to Cancer Mutation Pattern and Evolutionary Conservation.

The TP53 gene is frequently mutated in human cancer. Research has focused predominantly on six major "hotspot" codons, which account for only ∼30% of cancer-associated p53 mutations. To comprehensively characterize the consequences of the p53 mutation spectrum, we created a synthetically designed library and measured the functional impact of ∼10,000 DNA-binding domain (DBD) p53 variants in human cells in culture and in vivo.

The LATS2 tumor suppressor inhibits SREBP and suppresses hepatic cholesterol accumulation.

The Hippo signaling pathway is a major regulator of organ size. In the liver, Hippo pathway deregulation promotes hyperplasia and hepatocellular carcinoma primarily through hyperactivation of its downstream effector, YAP. The LATS2 tumor suppressor is a core member of the Hippo pathway.

Spatial behavior reflects the mental disorder in OCD patients with and without comorbid schizophrenia.

Objective: Resolving the entangled nosological dilemma of whether obsessive-compulsive disorder (OCD) with and without schizophrenia (schizo-OCD and OCD, respectively) are two independent entities or whether schizo-OCD is a combined product of its parent disorders.

Methods: Studying motor activity in OCD and in schizo-OCD patients. Performance of the patients was compared with the performance of the same motor task by a matching control individual.