Journal: Cancers

Article Title: Lactate Oxidase Disrupts Lactate-Activated RAS and PI3K Oncogenic Signaling.

doi: 10.3390/cancers16162817

Figure Lengend Snippet: Figure 7. Model of lactate and LOX regulation of the HCAR1-RAS/PI3K signaling cascades. TME lactate activates HCAR1, which induces the assembly of a protein complex that includes the receptor itself, GRB2, SOS1, RAS, GAB1, p85, and p110β. Subsequently, the RAS and PI3K pathways are acti- vated and transduce the lactate-triggered signals, via phosphorylated ERK1/2 and AKT, respectively, to the downstream transcription factors that further mediate the transcription of the genes involved in promoting the signaling and cancer cell survival and growth (left panel). Introducing LOX to the TME depletes lactate and renders HCAR1 inactive for triggering the assembly of the RAS and PI3K signaling complex. The disassembled HCAR1-associated RAS and PI3K signaling proteins are targeted for degradation by proteasomes (right panel). TME, tumor microenvironment; PM, plasma membrane; TF, transcription factor; the criss cross lines in the right panel represent removal or loss of interaction or signaling.

Article Snippet: Antibodies for HCAR (Abcepta, CA, USA), GRB2 (Santa Cruz Biotechnology, TX, USA), SOS1 (Proteintech, IL, USA), KRAS (Santa Cruz Biotechnology, TX, USA), GAB1 (Novus Biologicals, CO, USA), p85 (Proteintech, IL, USA), p110β (Cell Signaling Technology, MA, USA), p110α (Boster Bio, CA, USA), pERK1/2 (Santa Cruz Biotechnology, TX, USA), ERK1/2 (Santa Cruz Biotechnology, TX, USA), AKT (Cell Signaling Technology, MA, USA), pAKTS473 (Cell Signaling Technology, MA, USA), pAKTT308 (Cell Signaling Technology, MA, USA), MCT1 (Santa Cruz Biotechnology, TX, USA), MCT4 (Santa Cruz Biotechnology, TX, USA), and Actin (Thermo Scientific, MA, USA) were used in this study.

Techniques: Clinical Proteomics, Membrane