PTPN12 (Protein Tyrosine Phosphatase Non-Receptor Type 12)

These findings reveal the role of DUSP14 in regulating ferroptosis. Targeting DUSP14 represents a promising strategy for TNBC treatment.

Thirteen genes were associated with DCIS progression, and six genes were validated in the cell experiments. KEGG and GO analyses highlight TME's role in early breast cancer, enhancing understanding of DCIS occurrence and aiding identification of high-risk tumors.

Consistent with the mitotic stress caused by PTPN12 inactivation in TNBC cell lines, tumors harboring loss of PTPN12 exhibit heightened sensitivity to taxane chemotherapy. Collectively, this data suggests that PTPN12 inactivation may drive chromosomal instability and favorable MTA response in TNBC; two prominent features of the disease with unclear mechanistic etiology.

Using proteomics approaches, we uncovered Cofilin as a component of the phosphorylated integrin-Dok1 complex and linked this axis to effective invadopodia formation, a process supporting breast cancer invasion. These data further implicate dynamic modulation of integrin β1 phosphorylation at NPxY sites at different stages of metastatic dissemination.

These findings hold particular relevance for the Pakistani population, offering valuable insights into the genetic landscape of this aggressive cancer.

This highlights the mechanistic differences between PRLs and classical protein tyrosine phosphatases. Our findings refine our understanding of PRL catalysis and identify novel mutations for investigating PRL function in cancer and magnesium homeostasis.

Notably, treatment with the miR-369-3p inhibitor lowered the IC50 value for PC-9/AZD9291 cells; however, following downregulation of PTPN12 using PTPN12-siRNA, sensitivity due to low expression of miR-369-3p was significantly diminished (p < 0.05). miR-369-3p plays a crucial role in modulating drug resistance in PC-9/AZD9291 cells against osimertinib through regulation of PTPN12.

Further, we confirmed this protein-ligand binding using binding affinity studies based on protein thermal shift assay and in silico molecular dynamic simulations. Our efforts to discover a novel scaffold for inhibiting hPTP-PEST mark a crucial stride in laying the groundwork for the future development of selective PTP-PEST inhibitors.

Collectively, our findings indicate the involvement of circPTPN12 in modulating PDLIM2 function, influencing HCC progression. The identified ESRP1/circPTPN12/PDLIM2/NF-κB axis shows promise as a novel therapeutic target in the context of HCC.

Furthermore, mammary transgenic expression of phosphomimetic, cyclin-CDK-binding defective p27 (p27CK-DD) increases mammary duct branching morphogenesis, yielding hyperplasia and microinvasive cancers that can metastasize to liver, further supporting a role for p27pTpT in CSC expansion. Thus, p27pTpT interacts with STAT3, driving transcriptional programs governing stem cell expansion or maintenance in normal and cancer tissues.

P2, N=3, Terminated, Xiang Zhang | Withdrawn --> Terminated; Terminated by sponsor due to lack of interest

Subsequent experiments validated PTPN12, a master regulator of oncogenic receptor tyrosine kinases (RTKs), as a previously unrecognized negative regulator of the Hippo pathway effectors, oncogenic YAP/TAZ, influencing breast cancer cell proliferation and migration. In summary, our findings offer valuable insights into the roles of PTPs in the Hippo signaling pathway, significantly contributing to our understanding of breast cancer biology and potential therapeutic strategies.