Discovery of a new tumor suppressor previously thought to be an oncogene

August 8, 2018, The National Centre for Cancer Research
PLK1 overexpression pervents cell division thereby impairing cell proliferation and tumor growth. Credit: CNIO

The PLK1 gene, which has for decades been considered a tumor promoter, can also halt the development of cancer. This finding was made by researchers from the Spanish National Cancer Research Centre (CNIO) and Germany's Cancer Research Centre (DKFZ), who have published their results in the journal Nature Communications. The role of PLK1 as a target for powerful drugs must now be reviewed, since the value of inhibition depends on the tumor type. For the time being, the scientists have discovered that the expression of PLK1 in breast tumors can determine a different prognosis, depending on the tumor subtype.

The PLK1 gene is essential for the division and proliferation of cells. It has been known for years the overexpression of PLK1 is found in a large variety of tumor types, and on occasion, this overexpression is associated with poor prognosis (when a gene is overexpressed in the cell, there is an excess of the protein produced by that gene). For that reason, PLK1 has for decades been considered an oncogene, promoting the development of tumors. Plk1 is also a therapeutic target, since inhibiting its activity induces the death of cell tumors. In fact, there are Plk1 inhibitors already at advanced clinical stages.

Curiously, the oncogenic nature of PLK1 has never been formally demonstrated. In other words, until now, no experiment has been designed to demonstrate that the overexpression of PLK1 does indeed contribute to tumor development. That was the initial aim of researchers from Spain's National Cancer Research Centre (CNIO—Madrid) and Germany's Cancer Research Centre (DKFZ—Heidelberg) at the start of this joint research project.

They modified the genome of a mouse to overexpress the PLK1 gene at will. The first thing the researchers noted was that the mice did not develop any more tumors than normal mice. They then crossed their mice with others that expressed the oncogenes H-Ras or Her2 in breast tissue, and they developed very aggressive breast tumors. They expected a much greater incidence of , but the result was unexpected: by overexpressing PLK1 together with the oncogenes, the incidence of tumors was reduced drastically.

"That was when we realised that something important was happening," explained Guillermo de Cárcer, one of the lead researchers. "And in effect, we have shown that not only does PLK1 not act as an oncogene, but surprisingly, it acts as a ."

Plk1 as an indicator of breast cancer prognosis

Intrigued, the researchers consulted the breast cancer databases, in search of a link between the expression of PLK1 and patient prognosis. And they confirmed that "the expression of Plk1 can result in a very different type of prognosis depending on the tumor sub-type," said de Cárcer.

In Her2 positive tumors, the expression of PLK1 gives a better prognosis; however, in patients with positive tumors for the expression of the oestrogen receptor (ER+), it's the complete opposite. Not only does this paper describe the novel action of PLK1 as a tumor suppressor, it also identifies the molecular mechanism of this suppression. "We have seen that the overexpression of PLK1 increases the number of chromosomes in cells, because after they divide, cells cannot correctly segregate their chromosomes," said Rocío Sotillo, lead researcher with the Molecular Thoracic Oncology Group at DKFZ.

The fact that Plk1 acts as a tumor suppressor could call into question therapeutic strategies based on the inhibition of Plk1. However, Marcos Malumbres, head of the Cell Division and Cancer Research Group at CNIO and coordinator of the paper, trusts that the inhibition of Plk1 is still a valid and useful option.

"The fact that Plk1 is a tumor suppressor instead of an oncogene does not mean that Plk1 inhibitors will not be effective against cancer," said Malumbres. "Many essential components in cell proliferation can be used as targets against cancer despite lacking oncogenic activity, owing to the addition of cancer to specific cell processes such as cell division."

The work of these researchers evaluates the PLK1 gene as an oncological biomarker: "Understanding when PLK1 acts as an oncogene or as a tumor suppressor, and in which types of tumors this happens, is clinically extremely relevant when it comes to using this gene as a therapeutic biomarker," says Guillermo de Cárcer.

Explore further: Researchers discover that molecule considered to be a breast cancer indicator also has protective function

More information: Guillermo de Cárcer et al. Plk1 overexpression induces chromosomal instability and suppresses tumor development, Nature Communications (2018). DOI: 10.1038/s41467-018-05429-5

Related Stories

Researchers discover that molecule considered to be a breast cancer indicator also has protective function

June 26, 2013
(Medical Xpress)—One of the main indicators for determining the activity of a tumour or cancer is cell division. Cancer cells divide more than other types and the genes and molecules involved in the process of division ...

Team targets tumor suppressor to treat 'triple-negative' breast cancer

February 5, 2018
A study by scientists at the University of Arizona Cancer Center and Cancer Research UK has found that the loss of a specific tumor suppressor in "triple-negative" breast cancer provides clues about potential new approaches ...

Researchers uncover process that drives prostate cancer metastasis

April 21, 2016
Researchers at VCU Massey Cancer Center have uncovered a novel function of the gene PLK1 (polo-like kinase 1) that helps prostate cancer cells metastasize (spread) to other parts of the body. This mechanism highlights new ...

Scientists link new cancer treatments to cardiovascular alterations

July 10, 2017
Plk1 inhibitors have recently been acknowledged as an innovative therapy for leukaemia by the U.S. Food and Drug Administration (FDA). However, a study published in Nature Medicine by researchers from the Spanish National ...

Recommended for you

Week 34 of pregnancy reduces breast cancer risk: study

October 23, 2018
Women's bodies undergo a "striking" change during a specific week of pregnancy that can significantly reduce their risk of developing breast cancer later in life, scientists said Tuesday.

New kind of compound shows early promise against prostate cancer

October 23, 2018
A new type of molecule blocks the action of genes that drive the growth of therapy-resistant prostate cancer, a new study finds.

New combination treatment flips the switch on melanoma cells

October 23, 2018
Think of the protein BH3 like a finger that turns off a cancer cell survival switch. The problem is that most cancer cells have found ways to remove this "finger—commonly, by breaking the action of a gene called p53 that ...

Desperate & duped? GoFundMe means big bucks for dubious care

October 23, 2018
People seeking dubious, potentially harmful treatment for cancer and other ailments raised nearly $7 million over two years from crowdfunding sites, a study found.

Marker found for condition that causes numerous tumors

October 23, 2018
UT Southwestern researchers have made a major advance in uncovering the biology of how thousands of disfiguring skin tumors occur in patients troubled by a genetic disorder called neurofibromatosis type 1 (NF1). This scientific ...

Urban and rural rates of childhood cancer survival the same, study finds

October 23, 2018
Childhood and adolescent cancer survival in the United States does not vary by rural/urban residence at the time of diagnosis, finds a new study from the Brown School at Washington University in St. Louis.


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.