LEUKEMIA: INTRACELLULAR CHANGES IN LRP-1 RECEPTOR TRAFFIC AND AUTOPHAGIC RESPONSE.

GROSSO RA; SÁNCHEZ MC; CHIABRANDO GA; COLOMBO MI.; FADER CM

Buenos Aires

Congreso; Reunión conjunta de las sociedades de Biociencias; 2017

Modification of cell membrane proteins is an important event during erythropoiesis. Under maturation stimulus, erythoid cells active intracellular process such as, nuclear extrusion, autophagy of non-necessary organelles and regulating membrane protein. In leukemia cells this maturation response is impaired. Low density lipoprotein related-receptor protein-1 (LRP1) is a transmembranereceptor involved in numerous mechanism of cancer cells like migration, survival and apoptosis regulation. We recently emonstratedthat hemin (a maturation inductor) can stimulate erythroleukemia cells and activate autophagy and elimination of mitochondria. LRP1is responsible of hemin cellular uptake. The aim of our work is to study whether hemin is able to stimulate LRP-1 traffic and by thisregulate important intracellular changes in chronic leukemia cells through LRP1 signal. For this we performed an intracellular localization of LRP1 by immunofluorescence of K562 leukemia cell line. Different vesicles of endocytic and autophagic pathway were tagged with specific proteins such as Rab5, Rab7, Rab11, CD63, lysosomes and autophagosomes. Also a Golgi marker was used. We evaluate both early and late times. Moreover we study if hemin stimulates autophagy though LRP1 by western blot using silencing RNA against them and measuring levels of LC3-II protein (specific for autophagy). Importantly our results showed that hemin significantly modifies LRP1 normal intracellular localization from early endosomes and recycling vesicles to late endosomes and lysosomes in a time dependent manner. Likewise LRP1 is associated to autophagic vesicles under hemin incubation and its silencing downregulate over 50% the autophagic response. Taken together this results led us to think that hemin could regulate LRP1 activity and that this receptor is involved in crucial process as autophagy in leukemia cells. LRP1 modification may be important in cancer malignancy prognosis and therapeutics advances.