PTEN is a protein phosphatase that targets active PTK6 and inhibits PTK6 oncogenic signaling in prostate cancer

Wozniak, Darren J.; Kajdacsy-Balla, André; Macias, Virgilia; Ball-Kell, Susan; Zenner, Morgan L.; Bie, Wenjun; Tyner, Angela L.

doi:10.1038/s41467-017-01574-5

Cited by 69 publications

(56 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, the loss of PTEN, which occurs in the major of the tumors, is correlated with tumor aggressiveness and low response to therapy. In prostate cancer studies, PTEN has been shown to ameliorate the malignant phenotype by dephosphorylating the activator residue of PTK6 (Tyr 342), a kinase related to a cancer aggressive phenotype [94]. In addition, other oncogenic kinases, such as PDGFR and FAK, have been reported as a substrate of PTEN [95,96].…”

Section: Ptps That Act As Tumor Suppressorsmentioning

confidence: 99%

Protein Tyrosine Phosphatases in Tumor Progression and Metastasis: Promoter or Protection?

Ferreira-Halder¹,

Clerici²,

Faria³

et al. 2020

Tumor Progression and Metastasis

View full text Add to dashboard Cite

Reversible phosphorylation of proteins, executed by kinases and phosphatases, is the major posttranslational protein modification in eukaryotic cells, causing them to become activated or deactivated. This intracellular event represents a critical regulatory mechanism of several signaling pathways and can be related to a broad number of diseases, including cancer. Few decades ago, protein tyrosine phosphatases (PTPs) were considered as tumor suppressors. However, nowadays, accumulating evidence demonstrates that a misregulation of PTP activities plays a crucial and decisive role in cancer progression and metastasis. In this chapter, we will focus on the molecular aspects that support the crucial role of PTPs in cancer and in turn make them promising for prediction, monitoring, and rational appropriate therapy selection of individual patients.

show abstract

Section: Ptps That Act As Tumor Suppressorsmentioning

confidence: 99%

Protein Tyrosine Phosphatases in Tumor Progression and Metastasis: Promoter or Protection?

Ferreira-Halder¹,

Clerici²,

Faria³

et al. 2020

Tumor Progression and Metastasis

View full text Add to dashboard Cite

show abstract

“…When we inspected the data from the p110α overexpression study, we noted that ~10% of variants were not scored with high confidence. For example, the G129R mutation is well characterized as having a complete loss of PTEN function [32,33]. Yet in the p110α study it was not classified as a likely damaging with high confidence.…”

Section: Comparison With Existing Variant Analysesmentioning

confidence: 99%

Sentinel Interaction Mapping (SIM) – A generic approach for the functional analysis of human disease gene variants using yeast

Young

Post

Chao

et al. 2020

Preprint

View full text Add to dashboard Cite

Advances in sequencing technology have led to an explosion in the number of known genetic variants of human genes. A major challenge is to now determine which of these variants contribute to diseases as a result of their effect on gene function. Here we describe a generic approach using the yeast Saccharomyces cerevisiae to quickly develop gene-specific in vivo assays that can be used to quantify the level of function of a genetic variant. Using Synthetic Dosage Lethality screening, "sentinel" yeast strains are identified that are sensitive to overexpression of a human disease gene. Variants of the gene can then be functionalized in high-throughput fashion through simple growth assays using either solid or liquid media.Sentinel Interaction Mapping (SIM) has the potential to create functional assays for the large majority of human disease genes that do not have a yeast orthologue. Using the tumour suppressor gene PTEN as an example, we show that SIM assays can provide a fast and economical means to screen a large number of genetic variants.

show abstract

“…Moreover, we found that PTK6 and SRMS within the same upstream module. The product of two genes work closely together as intracellular kinases (32) and promotes invasive prostate cancer (33). However, they are rarely studied in the context of glioma and immune response.…”

Section: Orn Characterized Common Mechanisms In Cancermentioning

confidence: 99%

ORN: Extracting Latent Pathway Activities in Cancer with OR-gate Network

Liang

Zhu²,

2020

Preprint

View full text Add to dashboard Cite

Pathway level understanding of cancer plays a key role in precision oncology. In this study, we developed a novel data-driven model, called the OR-gate Network (ORN), to simultaneously infer functional relationships among mutations, patient-specific pathway activities, and gene co-expression. In principle, logical OR gates agree with mutual exclusivity patterns in somatic mutations and bicluster patterns in transcriptomic profiles. In a trained ORN, the differential expression profiles of tumours can be explained by somatic mutations perturbing signalling pathways. We applied ORN to lower grade glioma (LLG) samples in TCGA and breast cancer samples from METABRIC. Both datasets have shown pathway patterns related to immune response and cell cycles. In LLG samples, ORN identified multiple metabolic pathways closely related to glioma development and revealed two pathways closely related to patient survival. Additional results from the METABRIC datasets showed that ORN could characterize key mechanisms of cancer and connect them to less studied somatic mutations (e.g., BAP1, MIR604, MICAL3, and telomere activities), which may generate novel hypothesis for targeted therapy.

show abstract

PTEN is a protein phosphatase that targets active PTK6 and inhibits PTK6 oncogenic signaling in prostate cancer

Cited by 69 publications

References 64 publications

Protein Tyrosine Phosphatases in Tumor Progression and Metastasis: Promoter or Protection?

Protein Tyrosine Phosphatases in Tumor Progression and Metastasis: Promoter or Protection?

Sentinel Interaction Mapping (SIM) – A generic approach for the functional analysis of human disease gene variants using yeast

ORN: Extracting Latent Pathway Activities in Cancer with OR-gate Network

Contact Info

Product

Resources

About