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Printable Handouts
Navigable Slide Index
- Introduction
- Hallmarks
- KV10.1 is undetectable in peripheral tissues
- KV10.1 expression correlates with cancer outcome
- KV10.1 expression is cyclic and maximal in G2/M
- This observation opens two questions
- KV10.1 expression in healthy tissues
- What is the role of KV10.1 during G2/M?
- KV10.1-/- accelerates microtubule dynamics
- The changes in microtubule dynamics correlate with the frequency of cytoplasmic Ca2+ oscillations
- Cytoplasmic Ca2+ oscillations depend on KV10.1 and Orai1
- Primary cilium disassembly
- KV10.1 colocalizes with centrosomal proteins
- KV10.1 colocalizes with centrosomal proteins: density gradient
- KV10.1 is detected at the centrosome in living cells
- Asymmetric distribution of KV10.1
- KV10.1 localization at the (retracting) primary cilium
- Depletion/inhibition of KV10.1 delays ciliary resorption
- Cells from KV10.1-/- mice show increased frequency of cilia
- KV10.1 overexpression decreases the frequency of ciliated cells
- Cells from KV10.1-/- mice show increased frequency of cilia and altered SHH signaling
- Gain of function mutations result in a phenotype with clinical features reminiscent of ciliopathies
- Therapeutic opportunities targeting KV10.1
- KV10.1 expression correlates with outcome in cancer
- KV10.1 inhibition reduces tumor progression
- Inhibition of tumor growth is insufficient for tumor regression:
- Combinational approaches KV10.1-/- induces mitochondrial fragmentation
- Blockade of KV10.1 also induces mitochondrial fragmentation
- Mitochondrial inhibitors are more effective against KV10.1-positive cancer cells
- Use of KV10.1 expression to deliver TRAIL to the tumor cells
- scFv62-TRAIL sensitizes tumor cells to doxorrubicin
- Improved scTRAIL constructs and models (1)
- Improved scTRAIL constructs and models (2)
- Acknowledgments
Topics Covered
- Frequent ectopic expression of Kv10.1 in solid tumors
- Regulation of Kv10.1 expression along the cell cycle
- Role of Kv10.1 in calcium homeostasis during mitosis
- Kv10.1 and the primary cilium
- Implications for the pathology of gain of function mutations
- Participation of Kv10.1 in mitochondrial dynamics
- Therapeutic opportunities targeting Kv10.1
Talk Citation
Pardo, L. (2023, November 30). Kv10.1 potassium channels in cancer [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved December 23, 2024, from https://doi.org/10.69645/SOFK1226.Export Citation (RIS)
Publication History
Financial Disclosures
- There are no commercial/financial matters to disclose.
A selection of talks on Cell Biology
Transcript
Please wait while the transcript is being prepared...
0:00
Hello. This is a talk recorded
on behalf of Luis Pardo,
a scientist at the
Max Planck Institute
for Multidisciplinary Sciences
in Göttingen, Germany.
An institute focusing mainly on
neuroscience and universal
neuroscience research.
Doctor Pardo and his
team discovered that
voltage gated potassium channels
are relevant for cancer,
and that is the focus
of today's talk.
The title of the talk is K_v
10.1 potassium
channels in cancer.
Which is an expansion
and an update of
an older talk recorded
approximately 10 years ago.
0:34
The main feature highlighted
today is that K_v
10.1 is
a bona fide voltage gated
potassium channel
expressing neurons.
It opens in response to membrane
potential depolarization
and decreases neuronal
excitability.
It is abundantly expressed
in the human brain,
but it is not detectable
in non neural tissues.
From a pathological
point of view,
there are genetic diseases
that imply a gain of function,
mutation of the channel,
and result in problems
in the development and
a different
neurological phenotype
with different
forms of epilepsy.
But what's relevant for the talk
today is that the channel,
although it is a brain
potassium channel,
is very frequently
expressed in tumor tissues.
When it is expressed
in tumor tissues,
it provides the tumor cells with
a selective advantage in
such a way that at the end
of the evolution of a tumor,
you typically see a very
homogeneous expression
in the vast majority
of tumor cells.
Since it is so
abundantly expressed and
normally it is not expressed in
the tissue where the
tumor originated,
The potassium channel has
potential as a
therapeutic target.
1:39
The next slide summarizes
the evidence that
K_v 10.1 is abundantly
expressed in the brain.
In the left part of the slide,
you can see a real time PCR and
the mRNA expression in
different tissues of humans.
If you normalize and set
the value of expression
in the brain to one,
you can see that
there is a little bit
of expression maybe
in the spinal cord,
which could even be contaminated
by higher level tissues,
but it is essentially
absent from all other
normal tissues.
Then on the right side, there
is a table with a series of
determinations of the
expressions of K_v 10.1 protein.
There is some
immunohistochemistry in
clinical tumors from
different origins,
from biobanks and
clinics that has been
done by Dr. Pardo's lab in
the majority of the cases.
It has also been done in
other laboratories which
confirmed the finding
that over 70% of
all human carcinomas and
sarcomas express K_v
10.1 The only cancer that has
low expression of the channel in
studies is chronic leukemia.