Anti-PIK3CA (mutation E545K) Polyclonal Antibody

PI3K-Akt: This ancient signalling system, via receptor tyrosine kinases, controls cell proliferation, growth, survival metabolism and angiogenesis in the vast majority of solid tumours. The heterodimer of PI3K consists of a catalytic part p110 and a regulatory part p85. The catalytic subunit P110α of the PI3K complex PIK3CA is a too-often seen oncogenic mutation that is required for the formation and progression of solid tumours. In the PI3K-Akt signalling network, PI3K serves to fire PIP₂ into PIP₃. PIP₃ is one of the intracellular second messengers that PDK1 recognises and induces AKT. Once turned on, AKT can phosphorylate multiple downstream signalling or transcription factors that control a range of physiological cell functions.

Figure 1. Summary of functional roles and effectors of PI3Kα
(Source: Arafeh R, et al. 2019)

PIK3CA mutations trigger the PI3K-Akt cascade, which causes tumour cells to signal differently and create tumours and drug resistance. As many as a third of all human solid tumours are mutational PIK3CA – colorectal, gastric, cervical, breast, lung and other cancers. This gene PIK3CA was located on chromosome 3q and has five domains, an adaptor-binding domain, Ras-binding domain, C2 domain, helical domain, and kinase domain. More than 80% of PIK3CA mutations are found in the helical and kinase domains.ream signalling or transcription factors that regulate many of the activities of physiological cells. These are hotspot mutations in the helical domain: E542K, E545A, E545D, E545G, E545K and E545V. We know that there can be various mutations that cause PI3K activation in the different direction. E545K, E542K elicit PI3K via Ras-GTP, H1047R do not need Ras-GTP to initiate PI3K, they require p85 to initiate PI3K. Also, E545K mutation can also bind directly to insulin receptor substrate 1 protein to modulate AKT signaling pathway activity. The H1047R mutation, on the other hand, can modify conformation so that PI3K phosphorylates PIP2, which turns on the PI3K-Akt network.

The PIK3CA mutations make the tumour cells proliferative and invaders, and depress apoptosis. The PIK3CA gain-of-function mutations dysregulated activation of the PI3K-Akt signalling system that's a tumour marker for drug resistance today. Mutations in PIK3CA, for example, activate the PI3K-Akt pathway that makes breast cancer cells intolerant of endocrine therapy. PIK3CA mutations also make them resistant to some anticancer medications. PIK3CA mutations in colorectal, non-small cell lung and head and neck squamous cell carcinoma turn off the PI3K-Akt switch and make them resistant to tyrosine kinase.