triggers megakaryocytic differentiation in chronic myeloid leukemic cells, K562, through the increase if ganglioside GM3 content
Poster
Data di Pubblicazione:
2008
Citazione:
triggers megakaryocytic differentiation in chronic myeloid leukemic cells, K562, through the increase if ganglioside GM3 content / B. Lupo, C. Tringali, F. Cirillo, N. Papini, L. Anastasia, E. Monti, G. Tettamanti, B. Venerando - In: 53rd National Meeting of the Italian Society of Biochemistry and Molecular Biology (SIB) and National Meeting of Chemistry of of Biological Systems Italian Chemical Society (SCI - Section CSB) : Palazzo dei Congressi di Riccione, 23rd-26th September 2008Firenze : Firenze University Press, 2008 Sep. - ISBN 978-88-8453-820-8. - pp. 9.8-9.8 (( Intervento presentato al 53. convegno National Meeting of the Italian Society of Biochemistry and Molecular Biology (SIB) and National Meeting of Chemistry of Biological Systems Italian Chemical Society (SCI - SectionCSB) tenutosi a Riccione nel 2008.
Abstract:
Chronic myeloid leukaemia (CML) is a paradigmatic
example of neoplasia in which a differentiation arrest
occurs during the myeloid lineage and a highly
proliferative malignant clone originates1. In the context of
cancer disease and differentiation, an ever-increasing
interest is being focused on sialidases and
sialoglycoconjugates since alterations in these fields are
directly interconnected to neoplastic transformation2. In
particular, the plasma-membrane associated sialidase
Neu3 over-expression, reported in several tumours, is
linked to apoptosis resistance phenomena. In this report,
we demonstrated that the silencing of Neu3 in the CML
K562 cells decreases proliferation rate and apoptosis
resistance in favour of a differentiation process.
K562 cells were transduced with a shRNA targeting
the coding region of Neu3, inserted in a lentiviral vector.
Neu3 silencing (-70 % as protein content and – 93 %, as
catalytic activity) gave rise to significant events. First of
all, cyclin D2 and Myc were much less expressed (- 40 %
and – 30 %, respectively) while p21 increased (+ 60 %);
as consequence, cell growth and [3H]thymidine
incorporation (- 47 %) diminished. Apoptosis resistance
toward chemotherapeutic molecules such as etoposide
and staurosporine decreased, accordingly to a concurrent
decrease of the anti-apoptotic protein Bcl2 (- 30 %) and to
an increase of the pro-apoptotic proteins Bax and Bad (+
17 % and + 32 %, respectively). Moreover, K562 cells
became able to differentiate toward the megakaryocytic
lineage as proved by the appearance of the
megakaryocytic markers CD10, CD44, CD41, CD61. This
important cascade of events was triggered by the
activation of the signalling pathways PLC-b2, PKC, RAF,
ERK1/2, RSK90, and JNK. The molecular connection
between Neu3 silencing and the activation of PLC-b2 has
to be searched in the significant increase of GM3 (+ 81
%), as demonstrated by the treatment of K562 cells with
brefeldin A which simulated a GM3-rich conformation.
Therefore, these results indicate that Neu3 plays a
decisive role in CML and could be an interesting target for
developing therapeutic strategies.
Tipologia IRIS:
03 - Contributo in volume
Elenco autori:
B. Lupo, C. Tringali, F. Cirillo, N. Papini, L. Anastasia, E. Monti, G. Tettamanti, B. Venerando
Link alla scheda completa:
Titolo del libro:
53rd National Meeting of the Italian Society of Biochemistry and Molecular Biology (SIB) and National Meeting of Chemistry of of Biological Systems Italian Chemical Society (SCI - Section CSB) : Palazzo dei Congressi di Riccione, 23rd-26th September 2008