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

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

CIudad Autónoma de Buenos Aires

Congreso; Reunion conjunta de Sociedades de Biociencias; 2017

SAIB en conjunto con 10 sociedades científicas en biociencias del país.

Modification of cell membrane proteins is an important eventduring erythropoiesis. Under maturation stimulus, erythoid cellsactive intracellular process such as, nuclear extrusion, autophagyof non-necessary organelles and regulating membrane protein. Inleukemia cells this maturation response is impaired. Low densitylipoprotein related-receptor protein-1 (LRP1) is a transmembranereceptor involved in numerous mechanism of cancer cells like migration,survival and apoptosis regulation. We recently demonstratedthat hemin (a maturation inductor) can stimulate erythroleukemiacells and activate autophagy and elimination of mitochondria. LRP1is responsible of hemin cellular uptake. The aim of our work is tostudy whether hemin is able to stimulate LRP-1 traffic and by thisregulate important intracellular changes in chronic leukemia cellsthrough LRP1 signal. For this we performed an intracellular localizationof LRP1 by immunofluorescence of K562 leukemia cell line.Different vesicles of endocytic and autophagic pathway were taggedwith specific proteins such as Rab5, Rab7, Rab11, CD63, lysosomesand autophagosomes. Also a Golgi marker was used. Weevaluate both early and late times. Moreover we study if hemin stimulatesautophagy though LRP1 by western blot using silencing RNAagainst them and measuring levels of LC3-II protein (specific forautophagy). Importantly our results showed that hemin significantlymodifies LRP1 normal intracellular localization from early endosomesand recycling vesicles to late endosomes and lysosomes in atime dependent manner. Likewise LRP1 is associated to autophagicvesicles under hemin incubation and its silencing downregulate over50% the autophagic response. Taken together this results led us tothink that hemin could regulate LRP1 activity and that this receptoris involved in crucial process as autophagy in leukemia cells. LRP1modification may be important in cancer malignancy prognosis andtherapeutics advances.