Featured Research

from universities, journals, and other organizations

Cancer and the Goldilocks Effect: Too much or too little of an enzyme promotes cancer

Date:
April 3, 2014
Source:
University of California, San Diego Health Sciences
Summary:
Too little or too much of an enzyme called SRPK1 promotes cancer by disrupting a regulatory event critical for many fundamental cellular processes, including proliferation, research has found. "To my knowledge, this is the first time it has been shown that a signal kinase behaves as a tumor suppressor or a promoter, depending upon its abundance in the same cell" said one researcher. "The point is that too much or too little are both bad."

Researchers at the University of California, San Diego School of Medicine have found that too little or too much of an enzyme called SRPK1 promotes cancer by disrupting a regulatory event critical for many fundamental cellular processes, including proliferation.

The findings are published in the current online issue of Molecular Cell.

The family of SRPK kinases was first discovered by Xiang-Dong Fu, PhD, professor in the Department of Cellular and Molecular Medicine at UC San Diego in 1994. In 2012, Fu and colleagues uncovered that SPRK1 was a key signal transducer devoted to regulating alternative pre-mRNA splicing, a process that allows a single gene to produce multiple mRNA isoforms, which in many cases encode functionally distinct proteins. In this pathway, SRPK1 was a downstream target of Akt, also known as protein kinase B. Akt- activated SRPK1 moves to the nucleus to induce its targeted splicing factors.

In their latest paper, Fu and colleagues report that SRPK1 was found to act as a tumor suppressor because when ablated or removed from mouse embryonic fibroblasts, unwanted cell transformation occurred. Unexpectedly, when SRPK1 was overexpressed in mouse cells, tumor development also happened.

"To my knowledge, this is the first time it has been shown that a signal kinase behaves as a tumor suppressor or a promoter, depending upon its abundance in the same cell" said Fu. "The point is that too much or too little are both bad."

Such contrary phenomena are due to a surprising role of SRPK1 in regulating the activity of Akt via a specific Akt phosphatase discovered earlier by Alexandra C. Newton, PhD, professor of pharmacology at UC San Diego. The Akt phosphatase cannot find Akt when there is too little SRPK1 to assist, and the phosphatase is tied up when there is too much SRPK1. In both cases, the result is a dampening of Akt inactivation.

As Akt plays a key role in many cellular processes, such as glucose metabolism, apoptosis, proliferation and all key aspects of tumor development, the elucidated mechanism provides a critical insight into tumorigenesis in humans. Indeed, compared to normal cells, many tumors show SRPK1 overexpression while others display reduced expression.

The findings may have future therapeutic implications, but Fu said the challenges remain daunting. "Most tumors show SRPK1 overexpression, so it may be possible to treat certain cancers with a specific SRPK1 inhibitor. This has been already demonstrated by others. But suppressing a cancer not related to SRPK1 overexpression could actually stimulate that cancer."


Story Source:

The above story is based on materials provided by University of California, San Diego Health Sciences. Note: Materials may be edited for content and length.


Journal Reference:

  1. Pingping Wang, Zhihong Zhou, Anchang Hu, Claudio PontedeAlbuquerque, Yu Zhou, Lixin Hong, Emma Sierecki, Masahiko Ajiro, Michael Kruhlak, Curtis Harris, Kun-Liang Guan, Zhi-Ming Zheng, AlexandraC. Newton, Peiqing Sun, Huilin Zhou, Xiang-Dong Fu. Both Decreased and Increased SRPK1 Levels Promote Cancer by Interfering with PHLPP-Mediated Dephosphorylation of Akt. Molecular Cell, 2014; DOI: 10.1016/j.molcel.2014.03.007

Cite This Page:

University of California, San Diego Health Sciences. "Cancer and the Goldilocks Effect: Too much or too little of an enzyme promotes cancer." ScienceDaily. ScienceDaily, 3 April 2014. <www.sciencedaily.com/releases/2014/04/140403131742.htm>.
University of California, San Diego Health Sciences. (2014, April 3). Cancer and the Goldilocks Effect: Too much or too little of an enzyme promotes cancer. ScienceDaily. Retrieved July 22, 2014 from www.sciencedaily.com/releases/2014/04/140403131742.htm
University of California, San Diego Health Sciences. "Cancer and the Goldilocks Effect: Too much or too little of an enzyme promotes cancer." ScienceDaily. www.sciencedaily.com/releases/2014/04/140403131742.htm (accessed July 22, 2014).

Share This




More Health & Medicine News

Tuesday, July 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Gilead's $1000-a-Pill Drug Could Cure Hep C in HIV-Positive People

Gilead's $1000-a-Pill Drug Could Cure Hep C in HIV-Positive People

TheStreet (July 21, 2014) New research shows Gilead Science's drug Sovaldi helps in curing hepatitis C in those who suffer from HIV. In a medical study, the combination of Gilead's Hep C drug with anti-viral drug Ribavirin cured 76% of HIV-positive patients suffering from the most common hepatitis C strain. Hepatitis C and related complications have been a top cause of death in HIV-positive patients. Typical medication used to treat the disease, including interferon proteins, tended to react badly with HIV drugs. However, Sovaldi's %1,000-a-pill price tag could limit the number of patients able to access the treatment. TheStreet's Keris Lahiff reports from New York. Video provided by TheStreet
Powered by NewsLook.com
$23.6 Billion Awarded To Widow In Smoking Lawsuit

$23.6 Billion Awarded To Widow In Smoking Lawsuit

Newsy (July 20, 2014) Cynthia Robinson claims R.J. Reynolds Tobacco Company hid the health and addiction risks of its products, leading to the death of her husband in 1996. Video provided by Newsy
Powered by NewsLook.com
Tooth Plaque Provides Insight Into Diets Of Ancient People

Tooth Plaque Provides Insight Into Diets Of Ancient People

Newsy (July 19, 2014) Research on plaque from ancient teeth shows that our prehistoric ancestor's had a detailed understanding of plants long before developing agriculture. Video provided by Newsy
Powered by NewsLook.com
Contaminated Water Kills 3 Babies in South African Town

Contaminated Water Kills 3 Babies in South African Town

AFP (July 18, 2014) Contaminated water in South Africa's northwestern town of Bloemhof kills three babies and hospitalises over 500 people. The incident highlights growing fears over water safety in South Africa. Duration: 02:22 Video provided by AFP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins