Discovery of new code makes reprogramming of cancer cells possible
August 24, 2015 - Cancer researchers dream of the day they can force tumor cells to morph back to the normal cells they once were. Now, researchers on Mayo Clinic's Florida campus have discovered a way to potentially reprogram cancer cells back to normalcy.
The finding, published in Nature Cell Biology, represents "an unexpected new biology that provides the code, the software for turning off cancer," says the study's senior investigator, Panos Anastasiadis, Ph.D., chair of the Department of Cancer Biology on Mayo Clinic's Florida campus.
That code was unraveled by the discovery that adhesion proteins -- the glue that keeps cells together -- interact with the microprocessor, a key player in the production of molecules called microRNAs (miRNAs). The miRNAs orchestrate whole cellular programs by simultaneously regulating expression of a group of genes. The investigators found that when normal cells come in contact with each other, a specific subset of miRNAs suppresses genes that promote cell growth. However, when adhesion is disrupted in cancer cells, these miRNAs are misregulated and cells grow out of control. The investigators showed, in laboratory experiments, that restoring the normal miRNA levels in cancer cells can reverse that aberrant cell growth.
"The study brings together two so-far unrelated research fields -- cell-to-cell adhesion and miRNA biology -- to resolve a long-standing problem about the role of adhesion proteins in cell behavior that was baffling scientists," says the study's lead author Antonis Kourtidis, Ph.D., a research associate in Dr. Anastasiadis' lab. "Most significantly, it uncovers a new strategy for cancer therapy," he adds.
That problem arose from conflicting reports about E-cadherin and p120 catenin -- adhesion proteins that are essential for normal epithelial tissues to form, and which have long been considered to be tumor suppressors. "However, we and other researchers had found that this hypothesis didn't seem to be true, since both E-cadherin and p120 are still present in tumor cells and required for their progression," Dr. Anastasiadis says. "That led us to be believe that these molecules have two faces -- a good one, maintaining the normal behavior of the cells, and a bad one that drives tumorigenesis."
Their theory turned out to be true, but what was regulating this behavior was still unknown. To answer this, the researchers studied a new protein called PLEKHA7, which associates with E-cadherin and p120 only at the top, or the "apical" part of normal polarized epithelial cells. The investigators discovered that PLEKHA7 maintains the normal state of the cells, via a set of miRNAs, by tethering the microprocessor to E-cadherin and p120. In this state, E-cadherin and p120 exert their good tumor suppressor sides.
However, "when this apical adhesion complex was disrupted after loss of PLEKHA7, this set of miRNAs was misregulated, and the E-cadherin and p120 switched sides to become oncogenic," Dr. Anastasiadis says.
"We believe that loss of the apical PLEKHA7-microprocessor complex is an early and somewhat universal event in cancer," he adds. "In the vast majority of human tumor samples we examined, this apical structure is absent, although E-cadherin and p120 are still present. This produces the equivalent of a speeding car that has a lot of gas (the bad p120) and no brakes (the PLEKHA7-microprocessor complex).
"By administering the affected miRNAs in cancer cells to restore their normal levels, we should be able to re-establish the brakes and restore normal cell function," Dr. Anastasiadis says. "Initial experiments in some aggressive types of cancer are indeed very promising."
Siu Ngok, Ryan Feathers; Lomeli Carpio; Tiffany Baker; Jennifer Carr; Irene Yan; Sahra Borges, Edith Perez, Peter Storz, John Copland, Tushar Patel, E. Aubrey Thompson, Pamela Pulimeno, Sandra Citi. Distinct E-cadherin-based complexes regulate cell behaviour through miRNA processing or Src and p120-catenin activity. Nature Cell Biology, 2015 DOI: 10.1038/ncb3227
Top: Lead authors Panos Anastasiadis, Ph.D., and Antonis Kourtidis, Ph.D. Credit: Image courtesy of Mayo Clinic
Sustainable House Day 2015
Sustainable House Day, on Sunday 13 September 2015, is an international event where people who own houses that are doing good things with materials, energy, water and food, are opened up for any interested visitor to have a good long look at – to poke around, ask questions, and see for themselves.
It started in Australia, and has been going for about ten years, and over that period, tens of thousands of people have been inspired to ‘go and do likewise’. This is probably the most powerful tool we know of for educating and motivating people who know they want to do something, but are not quite sure what. And it’s something we all do – we see what somebody else has done, and say to ourselves “Hey – I can do that!”
THE TREEHOUSE - North Narrabeen, NSW
The owners of this award winning house wanted a sustainable home that would cater for their growing family and a separate granny flat for overseas visitors, all with a tree house feel. Lots of established trees, and steep land sloping away from the road contributed to the challenge of providing universal access to the main living […]
BEN BOYD ROAD HOUSE - Neutral Bay, NSW
Many sites have limited solar access, and are often written off as unsuitable for a low-energy high-comfort house. This should not be. This site in Neutral Bay, like many urban sites, had significant shading to the north, but we took advantage of one ‘window’ of north sun at ground level, and then ‘borrowed’ the rest from […]
WOY WOY BAY HOUSE - Woy Woy Bay, NSW
Originally a fishing shack dating back to the 1950s, there have been extensions in the 1960’s, 1970’s, and then a deck replacement in 2011. A primary goal for the 2011 renovation was to make the house more sustainable. This ongoing project has involved insulating both internal and external walls, while fibro (asbestos) cladding is removed and […]
You can see all the available houses at: sustainablehouseday.com
2014 NSW Coal Industry Profile, Volume 2 released
26th August 2015: NSW Government Department of Industry, Resources & Energy
Coal Industry Profile Vol 2The 2014 NSW Coal Industry Profile, Volume 2 is a companion to Volume 1 and provides further reference material up to the 2013–14 financial years on the NSW coal industry.
Volume 2 includes dossiers listings with extensive details on all existing and proposed mines, coal terminals, steelworks and coal-fired power stations in NSW.
Index listings of mines, company equity and equipment are also included.
This important reference guide will be available for purchase via the NSW Government Online shop and display as a convenient online e-book.
A subscription to 2014 NSW Coal Industry Profile, Volume 2 can be purchased for $150 via Shop NSW subscription form.
(Please note there will be no hard copy printed, as available in the past.)
More HERE
Katandra Sanctuary Open Days 2015
Katandra opens to the public every Sunday in July, August, September and October, from 10am to 4pm. The first will be Sunday July 5th with entry by donation.
See: Katandra Sanctuary Open Days 2015 by Marita Macrae
CALL TO RESEARCHERS WORLDWIDE TO SAVE HONEY BEES
Sydney says bye bye biosecurity beagles
The last biosecurity beagles at Sydney International Airport have said their farewells after years of service safeguarding Australia from exotic pests and diseases that could affect our way of life.
Minister for Agriculture, Barnaby Joyce, said beagles had served Australia well for more than 20 years as one of the surveillance technologies used to protect our agricultural industries, economy and environment.
"Our detector dog programme started in 1992, and since then beagles have been at our international airports sniffing out prohibited items such as seeds, plants, vegetables, fruit, eggs and meat with their keen sense of smell," Minister Joyce said.
"Now incoming passengers will be greeted by a labrador instead of a beagle.
"Travellers are sometimes unaware that plant and animal products, if not declared to biosecurity officers, could have a huge impact on our nation.
"We need travellers to think about what they're bringing into Australia, recognise the impact it could have and truthfully fill out the Incoming Passenger Card—which is a legal document.
"The five beagles we're honouring—TJ, Wally, Sharne, Axel and Andy—have all served Australia well.
"Collectively they've seized 29,799 items, weighing in at nearly 7 tonnes combined, from more than 100 countries.
"As a result of their sharp noses the five beagles have been responsible for 91 Quarantine Infringement Notices issued to travellers arriving in Australia."
Minister Joyce emphasised the important role travellers played in keeping Australia free from harmful pests and diseases.
"Managing Australia's biosecurity system to protect our plant, animal and human health is a big and important job," Minister Joyce said.
"Each year more than 17 million international passengers arrive in our airports, and our dedicated biosecurity staff screened 8.7 million of those in 2013–14—that's 24,000 a day.
"Our biosecurity beagles have potentially saved Australia from exotic diseases such as foot-and-mouth disease and equine influenza as well as countless others.
"These farewells are significant, as TJ, Wally, Sharne, Axel and Andy are the last working beagles at Sydney International Airport.
"As our last beagles retire, we're in the process of moving our canine workforce toward labradors, who are a more readily available and versatile breed, and are more suited to work across a range of locations.
"Andy, Wally and Axel will be using their expertise to help train new detector dog handlers up in Brisbane, while TJ and Sharne will enjoy some well deserved rest and relaxation in retirement with former handlers."
Top: Photo of Minister Joyce with Department of Agriculture dog handlers David Lister and Clare OShannessy and beagle TJ
Scholarship to help balance academia and parenthood Now Open at UNSW
19 AUG 2015: UNSW MEDICINE
Balancing parenthood with academia is set to become easier with a UNSW Medicine scholarship that helps early career women focus on research when returning to work after parental leave.
Scholarship named in her honour - Professor Minoti Apte OAM
The scholarship – named after NSW Premier’s Woman of the Year Professor Minoti Apte OAM – will provide eligible staff with relief from teaching and administration to write publications, applications and/or access research assistance. UNSW Medicine Dean Rodney Phillips said the scholarship – the first of its kind in the faculty – reinforces a long and proud tradition of employing and promoting female academics across all schools and affiliated research institutes.
“Some of the nation’s leading academics and researchers are also mothers and it is vital that we do everything we can to support women who are balancing parenthood with academia,” Professor Phillips said. Professor Phillips also highlighted the scholarship’s alignment to a University-wide commitment to a pilot of the Athena SWAN program; a highly successful UK-based charter established to encourage career advancement for women in higher education and research working in the fields of science, technology, engineering, maths and medicine (STEMM).
Professor Apte said she was thrilled the award was named in her honour and said supporting mothers to continue to flourish in their academic research career is vital. According to the latest Catalyst figures, women hold just 29.9% of ‘above senior lecturer’ positions in Australia.
“My path from medical student to senior academic while raising a family was challenging. I was lucky to have received a lot of support but inequality and disadvantage for women returning to work remains a big problem in Australia,” she said. “This scholarships shows that UNSW Medicine is leading the way in creating family-friendly workplace arrangements and supporting women who want to balance family with pursuing a career in science, academia or medical research.”
The idea for the scholarship came from Head of the School of Public Health and Community Medicine Professor Raina MacIntyre who has also experienced first-hand the challenge of juggling motherhood with a successful career in academia. “This scholarship is not only about providing mothers with time for research, it is also about sending female academics in the faculty the message that their research and career is important, and that retaining bright women in the workforce is a priority,” she said.
The first scholarship recipient is expected to be announced in November 2015. The maximum amount available per scholarship will be $20,000. Applications close 30 September 2015. For more detailed information go to: unsw.edu.au/academic-women-unsw-medicine