Abstract A040: Suppressing the cytomatrix elastic solid phase of cytoplasm will eliminate the root cause of cancer

Abstract

Abstract The Warburg effect, the increase of glucose uptake rate and lactate production, is a tremendous metabolic switch, a prominent cancer hallmark, and a century-old mystery. We recently solved an age-old problem of biochemistry, how myriad diverse chemical reactions coincide in the cell, by chemically separating elastic solid (cytomatrix) and viscous fluid (cytosol) phases of cytoplasm (iScience, 2023, PMID:36824274) that can elucidate a role of the Warburg effect in tumors. Biochemical reactions within the cytoplasm are catalytic and performed by enzyme complexes. Catalytic complexes are immobilized on the solid platform, and the cytomatrix physically separates them from each other, but the substrate delivery mechanisms have remained unknown. Using the multiomic approach, we found that cytomatrix proteins actomyosins are responsible for cellular micromechanics and cytosolic motion. Cytosolic motion delivers substrates to catalytic complexes. Cytomatrix micromechanics requires energy maintained by mitochondrial respiration in physiological conditions. However, due to mutational and epigenetic alterations, malignant cells need additional energy to stir biochemical processes. Actomyosin and actin-binding and regulating proteome, a structural base of the cytomatrix and primary motor proteins, exploits aerobic glycolysis to meet the energy demand of cytomatrix, just as muscle fiber utilizes the aerobic glycolysis during intense exercise. Therefore, synchronizing energy output for cytomatrix micromechanics is a limiting step for the malignant transformation involving the Warburg effect. Unless mutations coalesce with the increased energy production for cytomatrix mechanics, potential cancer may only survive in the quiescent state (or benign), or it will be eliminated. Cancer development appears to be a two-sided coin relying on both the mutation and the energy demand, suggesting that not everyone gets cancer with the same mutation without the involvement of aerobic glycolysis. By uniting the Warburg effect with the cytomatrix micromechanics and genetic and epigenetic alterations, our concept of cancer development better explains the transformation of healthy cells to malignant cells and malignant cell resistance to therapy and recurrence. Revealing the cytomatrix allowed us to find its practical application. We developed technology that works on the cytomatrix level and can improve cancer treatment and prevent tumor recurrence. Suppression of the cytomatrix activity will inhibit cancer resistance and recurrence and increase the efficiency of the current anticancer therapy. It is impossible to know if cancer will return after treatment. Cancers come back when small numbers of malignant cells can remain in the body after treatment. These cells are too rare to find with current tests. We have developed a method to help detect this small number of malignant cells. Our fast and sensitive method can isolate malignant cells from a frozen biopsy about 10 – 20 mg weight. Thus, revealing the cytomatrix opens a new chapter in cancer research and therapy. Citation Format: Tattym E. Shaiken. Suppressing the cytomatrix elastic solid phase of cytoplasm will eliminate the root cause of cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Cancer Evolution and Data Science: The Next Frontier; 2023 Dec 3-6; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_2):Abstract nr A040.