Dec

25

Inhibition of mitochondrial mobility may

be the key to preventing metastasis

The tumor cells position their mitochondria in their membranes to obtain the energy
necessary to leave the primary tumor and colonize other organs

Mitochondria are the organelles responsible for processing nutrients and oxygen to
generate energy for the cells. Mitochondria, that are the energy centers of each and
every healthy cell in the body, do not seem to have enough power to supply the needs of
tumor cells. Or at least, this has been believed in the past. However, a new study
conducted by researchers at the Wistar Institute in Philadelphia (USA) has identified a
new pathway which opens the door to the development of new treatments against
different types of cancer.

Dario C. Altieri as research director published in the journal Nature Communications ",
explains "the scientific community has been ignoring a fundamental aspect of
cancer metabolism because we have overlooked the role of mitochondria and
oxidative metabolic processes in oncological diseases. Our findings open the way for
new research in this field, although more studies are needed to evaluate the role of
mitochondria in tumor metabolism.

Mitochondrial positioning
Tumor cells have a high rate of proliferation and mobility, to migrate and colonize
other organs, that is, the process known as 'metastasis' they require more energy than
those of healthy cells. Consequently, these cancer cells can not subordinate their energy
supply to mitochondria and oxygen - whose concentration is minimal in tumor tissues
since it is rapidly consumed by cells and does not reach all - and must seek other
sources' alternatives'. A phenomenon known in the scientific world as the 'Warburg
effect', which has been confirmed in numerous studies, has caused the role of
mitochondria has traditionally been ignored in cancer research. A decision that now, as
the new study shows, seems completely wrong.

The new work shows that mitochondria in tumor cells are located near the cell
membrane and provide the energy for movement. A cellular behavior that until now
had only been observed in neurons.

Our study opens up new potential therapeutic options for metastatic disease.
The point is how tumor cells position the mitochondria next to their membranes? Just as
the neurons do, they use the proteins responsible for controlling mitochondrial
movement. To do this, they reprogram this protein network to 'transfer' the mitochondria
to the place where it's needed - in this case, close to the membrane.

Moreover, the study shows that one of the proteins in this network, called 'syntaphyllin'
(SNPH), inhibits tumor migration by inhibiting cell movement in prostate cancer cells.
Thus, and through inhibiting the expression of this protein, prostate tumor cells get
their mitochondria moved from their typical positions -around core CELLULAR-
to near areas membranes. And is this 'reprogramming' of sintafylline exclusive to
prostate cancer? Well, no. The evaluation of the levels of expression of the SNPH gene
in biopsies taken to patients with epithelial tumors and hematological diseases showed
that the reduced levels of syntaphylline are correlated with the progression of the
disease and, consequently, with a worse prognosis.

Stopping metastases
In short, the study confirms the important role mitochondria play in tumor development,
especially in distant organ metastases.

As Cecilia Caino, co-author of the research, explains "in our work we have been able to
establish a correlation between this protein pathway and the progression and survival of
the disease in different types of cancer, not only in the prostate. This indicates that we
are dealing with a general mechanism of suppression of metastasis. That is, it is not
specific to a single tumor type. Our findings have important clinical implications,
because some of the proteins of this network are susceptible to drugs and therefore
potential new therapeutic options for metastatic disease are opened. "
Publicado 25th December 2016 por Jorge Garca