Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Protein found to shield pancreatic cancer cells from self-destruction

An overexpressed protein protects human pancreatic cancer cells from being forced to devour themselves, removing one of the body's natural defenses against out-of-control cell growth, researchers at The University of Texas M. D. Anderson Cancer Center report in the March issue of Molecular Cancer Research.

The protein tissue transglutaminase, known by the abbreviation TG2, previously has been found by researchers at M. D. Anderson and elsewhere to be overexpressed in a variety of drug-resistant cancer cells and in cancer that has spread from its original organ (metastasized).

"In general, you rarely see overexpression of TG2 in a normal cell," says Kapil Mehta, Ph.D., professor in the M. D. Anderson Department of Experimental Therapeutics, who began 10 years ago studying TG2 as an inflammatory protein.

Mehta and colleagues in the past year have connected TG2 overexpression to drug-resistant and metastatic breast cancer, pancreatic cancer and melanoma.

... more about:
»Cancer »Mehta »Organelle »TG2 »autophagy »pancreatic

Expression of TG2 is tightly regulated in a healthy cell, Mehta says, and is temporarily increased in response to certain hormones or stress factors. "However, constitutive expression of this protein in a cancer cell helps confer protection from stress-induced cell death," Mehta says. "We are developing TG2 as a pharmaceutical target and are now working with a mouse model to that end."

The mechanisms by which TG2 might promote drug-resistance and metastasis have remained elusive, the researchers note. In this paper, the M. D. Anderson team shows in lab experiments that inhibiting the protein in pancreatic cancer cells leads to a form of programmed cell suicide called autophagy, or self-digestion.

TG2 was inhibited in two separate ways. First, the researchers blocked another protein known to activate TG2. Secondly, they also directly targeted TG2 with a tiny molecule known as small interfering RNA tailored to shut down expression of the protein.

In both cases, the result was a drastic reduction of TG2 expression (up to 94 percent) and telltale signs of autophagy in the cancer cells, which became riddled with cavities called vacuoles.

When autophagy occurs, a double membrane forms around a cell organ, or organelle. This autophagosome then merges with a digestive organelle called a lysosome and everything inside is consumed, leaving the vacuole and a residue of digested material. If enough of this happens, the cell dies.

Gabriel Lopez-Berestein, M.D., professor of experimental therapeutics and study co-author, notes that the research also shows that the self-consuming cell death prevented by TG2 is independent of a prominent molecular pathway also known to regulate autophagy called the mammalian target of rapamycin.

"Targeting TG2, or its activating protein PKC, or both, presents a novel and potentially effective approach to treating patients with pancreatic cancer," Lopez-Berestein said. Research in the mouse model remains in the early stages, the researchers caution.

The researchers also show that the TG2 pathway also is separate from another, better known, form of programmed cell death called apoptosis.

Apoptosis, like autophagy, is a normal biological defense mechanism that systematically destroys defective cells by forcing them to kill themselves. In apoptosis, the cells die via damage to their nucleus and DNA, with other cellular organelles preserved. Autophagy kills by degrading those other organelles while sparing the nucleus.

Mehta's lab reported in a Cancer Research paper last September that TG2 overexpression also activates a protein called nuclear factor-kB known to play a role in regulating cell growth, metastasis and apoptosis. This pathway, Mehta explained, could make TG2 an attractive target for other forms of cancer as well.

Scott Merville | EurekAlert!
Further information:

Further reports about: Cancer Mehta Organelle TG2 autophagy pancreatic

More articles from Life Sciences:

nachricht First time-lapse footage of cell activity during limb regeneration
25.10.2016 | eLife

nachricht Phenotype at the push of a button
25.10.2016 | Institut für Pflanzenbiochemie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Etching Microstructures with Lasers

Ultrafast lasers have introduced new possibilities in engraving ultrafine structures, and scientists are now also investigating how to use them to etch microstructures into thin glass. There are possible applications in analytics (lab on a chip) and especially in electronics and the consumer sector, where great interest has been shown.

This new method was born of a surprising phenomenon: irradiating glass in a particular way with an ultrafast laser has the effect of making the glass up to a...

Im Focus: Light-driven atomic rotations excite magnetic waves

Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion

Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Greater Range and Longer Lifetime

26.10.2016 | Power and Electrical Engineering

VDI presents International Bionic Award of the Schauenburg Foundation

26.10.2016 | Awards Funding

3-D-printed magnets

26.10.2016 | Power and Electrical Engineering

More VideoLinks >>>