Thyroid cancer is the most common endocrine
malignancy with increasing incidence worldwide. The
majority of thyroid cancer cases are well
differentiated with favorable outcome.
However, undifferentiated thyroid cancers are one of
the most lethal human malignancies because of their
invasiveness, metastatization and refractoriness
even to the most recently developed therapies.
In this study researchers show for the first time a
significant hyperactivation of ROCK/HDAC6 pathway in
thyroid cancer tissues, and its negative correlation
with p53 DNA binding ability.
Researchers demonstrate that a small compound,
SP600125 (SP), is able to induce cell death
selectively in undifferentiated thyroid cancer cell
lines by specifically acting on the pathogenic
pathways of cancer development.
In detail, SP acts on the ROCK/HDAC6 pathway
involved in dedifferentiation and invasiveness of
undifferentiated human cancers, by restoring its
physiological activity level.
As main consequence, cancer cell migration is
inhibited and, at the same time, cell death is
induced through the mitotic catastrophe.
Moreover, SP exerts a preferential action on the
mutant p53 by increasing its DNA binding ability. In
TP53-mutant cells that survive mitotic catastrophe
this process results in p21 induction and eventually
lead to premature senescence.
In conclusion, SP has been proved to be able to
simultaneously block cell replication and migration,
the two main processes involved in cancer
development and dissemination, making it an ideal
candidate for developing new drugs against
anaplastic thyroid cancer.
For more information
Oncotarget
SP600125 has a remarkable anticancer potential
against undifferentiated thyroid cancer through
selective action on ROCK and p53 pathways
DOI: 10.18632/oncotarget.5799
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