Stem cell protein offers a new cancer target

Jun 01, 2009

A protein abundant in embryonic stem cells is now shown to be important in cancer, and offers a possible new target for drug development, report researchers from the Stem Cell Program at Children's Hospital Boston.

Last year, George Daley, MD, PhD, and graduate student Srinivas Viswanathan, in collaboration with Richard Gregory, PhD, also of the Stem Cell Program at Children's, showed that the protein LIN28 regulates an important group of tumor-suppressing microRNAs known as let-7. Increasing LIN28 production in a cell prevented let-7 from maturing, making the cell more immature and stem-like. Since these qualities also make a cell more cancerous, and because low levels of mature let-7 have been associated with breast and lung , the discovery suggested that LIN28 might be oncogenic.

Now, publishing Advance Online in Nature Genetics on May 31, Daley, Viswanathan and colleagues show directly that LIN28 can transform cells to a cancerous state, and that it is abundant in a variety of advanced human cancers, particularly , , chronic myeloid leukemia, germ cell tumors and Wilm's tumor (a childhood ). They believe that overall, LIN28 and a related protein, LIN28B, may be involved in some 15 percent of human cancers. By blocking or suppressing LIN28, it might be possible to revive the let-7 family's natural tumor-suppressing action.

"Linking this protein to advanced cancer is a very exciting new result," says Daley, Director of Stem Cell Transplantation at Children's, and also affiliated with Children's Division of Hematology/Oncology, the Dana-Farber Cancer Institute and the Harvard Stem Cell Institute. "It gives us a new target to attack, especially in the most resistant and hard-to-treat cases."

LIN28, which is abundant in embryonic stem cells and prevents them from differentiating into specific cell types, was originally discovered to influence embryonic development in worms some 25 years ago. Development, stem cell generation and carcinogenesis are known to be closely related, but until last year's study connected LIN28 to let-7, it hadn't been clear how.

"LIN28 is a fascinating protein that acts both in stem cells and cancers, and is teaching us that cancer is often a disease of ," says Daley.

Viswanathan, Daley and colleagues are busily searching for ways to inhibit LIN28, which could provide promising new drugs for advanced cancer.

Source: Children's Hospital Boston (news : web)

Explore further: Throwing a loop to silence gene expression

add to favorites email to friend print save as pdf

Related Stories

Therapy may block expansion of breast cancer cells

Nov 05, 2008

Breast cancer stem cells are known to be involved in therapy resistance and the recurrence of cancerous tumors. A new study appearing in Clinical and Translational Science shows the mechanisms governing stem cell expansion in bre ...

Herceptin targets breast cancer stem cells

Jul 09, 2008

A gene that is overexpressed in 20 percent of breast cancers increases the number of cancer stem cells, the cells that fuel a tumor's growth and spread, according to a new study from the University of Michigan Comprehensive ...

Scientists isolate cancer stem cells

Sep 11, 2008

After years of working toward this goal, scientists at the OU Cancer Institute have found a way to isolate cancer stem cells in tumors so they can target the cells and kill them, keeping cancer from returning.

Recommended for you

Throwing a loop to silence gene expression

9 hours ago

All human cells contain essentially the same DNA sequence – their genetic information. How is it possible that shapes and functions of cells in the different parts of the body are so different? While every cell's DNA contains ...

A nucleotide change could initiate fragile X syndrome

Sep 01, 2014

Researchers reveal how the alteration of a single nucleotide—the basic building block of DNA—could initiate fragile X syndrome, the most common inherited form of intellectual disability. The study appears ...

Gene clues to glaucoma risk

Aug 31, 2014

Scientists on Sunday said they had identified six genetic variants linked to glaucoma, a discovery that should help earlier diagnosis and better treatment for this often-debilitating eye disease.

User comments : 0