Novel insights of how prostate cancer causes secondary tumors

Date:
September 3, 2020
Source:
Umea University
Summary:
An increased awareness on a molecular level of what mechanisms
prostate cancer cells use to become mobile and start spreading
may in the long run provide new opportunities for treatment of
aggressive prostate cancer.

This according to a new study by researchers at Umeaa University,
Sweden, in collaboration with researchers in Uppsala and Tokyo.



FULL STORY ==========================================================================
An increased awareness on a molecular level of what mechanisms prostate
cancer cells use to become mobile and start spreading may in the long
run provide new opportunities for treatment of aggressive prostate
cancer. This according to a new study by researchers at Umeaa University, Sweden, in collaboration with researchers in Uppsala and Tokyo.


==========================================================================
"We can show that one specific amino acid in a signalling molecule
plays an important role in mobilising the cancer cells and in that way
increase the risk of metastases," says Professor Mare'ne Landstro"m,
Umeaa University.

This research has studied the growth factor TGF-b, Transforming Growth
Factor Beta, which regulates how cells grow and specialise. Previous
studies have shown an overproduction of TGF-b in many cancer forms, one
being prostate cancer. High levels of TGF-b have proven to be strongly
linked with poor prognosis and low survival rates as a consequence of
the growth factor stimulating cancer cells to spread in the human body
and cause life-threatening secondary tumors -- so-called metastases.

TGF-b regulates the expression of the protein Smad7 -- an active
component in the TGF-b signalling chain. In healthy cells, Smad7 can
prevent continued TGF- b signalling via negative feedback. However,
Mare'ne Landstro"m and her research group and colleagues can now show,
contrary to previous belief, that, in cancer cells, Smad7 can reinforce
the development of tumors by regulating the gene expression of HDAC6
and c-Jun.

The specific amino acid that has caught the researchers' attention is
called Lys102 and is found in Smad7. This amino acid binds to particular
gene- regulating functions in DNA to increase production of the gene
expression HDAC6 and c-Jun. This has the effect that cancer cells become
more mobile and more prone to form metastases. Researchers have been
able to see a clear connection between all these variables and a negative prognosis for prostate cancer.

"The good news is that by using treatment with an HDAC6 inhibitor,
we can make prostate cancer cells lose their mobility. In that way,
novel opportunities can open up for treatments that reduce the risk of metastases," says Mare'ne Landstro"m.

Clinical trials are now taking place in the UK to find specific HDAC6 inhibitors in patients with solid tumors, which means that treatments
using HDAC6 inhibitors can become a complement in the cancer treatment of patients with hard-to-treat forms of disease. Future studies can explore
the benefit of indicating expressions of Smad7, HDAC6 and c-Jun to enable
new and more specific treatments for men with aggressive prostate cancer.

The study also shows an entirely new function of Smad7 in the way that it
can recruit Smad2 and Smad3 to the place of transcription for these genes.

Previously, it has been thought that Smad7 held the role of inhibitor
for TGF beta-Smad2/3 transcriptional activity.


========================================================================== Story Source: Materials provided by Umea_University. Original written
by Ola Nilsson. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Noopur Thakur, Anahita Hamidi, Jie Song, Susumu Itoh, Anders
Bergh, Carl-
Henrik Heldin, Mare'ne Landstro"m. Smad7 Enhances TGF-b-Induced
Transcription of c-Jun and HDAC6 Promoting Invasion of Prostate
Cancer Cells. iScience, 2020; 101470 DOI: 10.1016/j.isci.2020.101470 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/09/200903133015.htm

--- up 1 week, 3 days, 6 hours, 50 minutes
* Origin: -=> Castle Rock BBS <=- Now Husky HPT Powered! (1337:3/111)