Navigation Links
TRPM7 protein key to breast cancer metastasis in animal models
Date:8/7/2012

PHILADELPHIA The protein transient receptor potential melastatin-like 7 (TRPM7) is a critical determinant of breast cancer cell metastasis, according to study results published in Cancer Research, a journal of the American Association for Cancer Research.

"The most important discovery that we report in this paper is that TRPM7 is required for metastasis, at least in a xenograft model of breast cancer metastasis," said Frank van Leeuwen, Ph.D., assistant professor at the Radbound University Medical Center in Nijmegen, the Netherlands. "While this fundamental biological finding will not have an immediate impact on patient care, we believe that it opens the door to a previously under-explored area of cancer therapeutics.

"TRPM7 functions as a cation channel. As such, it is in a class of proteins that is already therapeutically targeted to treat diseases; for example, cation channel blockers are used to treat several heart conditions. Given that cation channels are druggable, our data provide clear rationale for probing whether drugs that target this class of proteins could block metastasis."

Central to tumor metastasis are changes in the capacity of tumor cells to adhere to other cells and tissue at the original tumor site and changes in their ability to migrate. As TRPM7 was known to be involved in regulating cell adhesion and migration, van Leeuwen and his colleagues, including researchers at The Netherlands Cancer Institute in Amsterdam, set out to investigate whether TRMP7 had a role in cancer cell metastasis.

They evaluated whether the level of expression of the TRPM7 gene correlated with breast cancer progression. In primary breast tumors removed at diagnosis from a cohort of 368 women, high levels of expression from the TRPM7 gene were associated with significantly shorter times to both recurrence of disease and occurrence of distant metastases. This association was validated in an independent cohort of 144 breast cancer patients.

"We were able to show that high levels of TRPM7 expression independently predicted poor patient outcome in these two cohorts of women," said van Leeuwen. "Whether this is useful for forecasting patient prognosis awaits further validation. Moreover, it has become increasingly clear that it is not possible to stratify breast cancer patients into prognostically meaningful groups based on the level of expression of a single gene. TRPM7 would, therefore, need to be part of a panel of markers predictive of metastasis."

Having established a clinically relevant link between TRPM7 levels and metastatic disease in breast cancer patients, van Leeuwen and his colleagues examined the underlying molecular mechanisms using in vitro and in vivo assays.

The results indicated that knocking down TRPM7 expression in invasive human breast cancer cells impaired their ability to migrate in vitro and their metastatic potential when transferred into mice. Further analysis pinned down molecular and cellular reasons for these observations.

"Our working hypothesis is that TRPM7 has a key role in the cross-talk that goes on between breast cancer cells and their environment," van Leeuwen said. "Breast cancer cells are very sensitive to environmental cues. We think, but have no formal proof as yet, that TRPM7 channels are sensors that enable breast cancer cells to perceive changes in their environment."


'/>"/>
Contact: Jeremy Moore
jeremy.moore@aacr.org
215-446-7109
American Association for Cancer Research
Source:Eurekalert

Related medicine news :

1. Vanderbilt researchers find proteins may point way to new prostate cancer drug targets
2. UNC team describes novel inflammatory protein function
3. In Mice, Alzheimers-Linked Protein Shows Promise Against MS
4. Protein-based coating could help rehabilitate long-term brain function
5. SFU duos protein discovery links to cancer research
6. Protein build-up leads to neurons misfiring
7. Strong communication between brain and muscle requires both having the protein LRP4
8. Regulation by proteins outside cancer cells points to potential new drug target
9. Loss of protein SPDEF allows prostate cancer cells to gain foothold at possible sites of metastasis
10. The key (proteins) to self-renewing skin
11. Researchers discover rare leukemia-causing protein
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/12/2016)... , ... February 12, 2016 , ... The law firm ... and Evangeline Parishes. The purpose of these scholarships is to encourage applicants to ... individuals to seek employment within these two parishes. , “We have available jobs ...
(Date:2/12/2016)... ... ... Each year, the American Physical Therapy Association (APTA) offers a Combined Sections ... Center. Almost 10,000 physical therapists across the country are expected to attend this annual ... chosen field and network with their colleagues. As in years past, HydroWorx is ...
(Date:2/12/2016)... ... February 12, 2016 , ... ... (WaaS), today announced the integration of Clarity Intelligence Platform (CIP) into Cielo®, a ... offer real-time business intelligence (BI) to their small and medium business (SMB) clients. ...
(Date:2/12/2016)... ... 2016 , ... Vail knee specialist Robert LaPrade, MD, PhD was ... The list consists of physicians establishing, leading and partnering with ambulatory surgery centers across ... Ambulatory Surgery Center, also known as an ASC, is a modern health care facility ...
(Date:2/12/2016)... ... 2016 , ... For Coast Dental dentist Everet Lake, DDS, the smiles began ... Moore shortly before 7 a.m. to volunteer at Friday’s Dentistry from the Heart event ... skills to help hundreds of uninsured and underinsured people receive much-needed dental care. ...
Breaking Medicine News(10 mins):
(Date:2/11/2016)... -- NOIT™ Research LLC, a private, leading-edge autism research group, ... assist needy families in obtaining one of its special ... 10, 2016 and March 31, 2016, the company will ... is an auditory stimulus that plays a key role ... Beth Shier , NOIT Research director. "The ...
(Date:2/11/2016)... N.C. , Feb. 11, 2016 ... leading provider of custom manufacturing and development services ... expanded sterile fill-finish capabilities and capacity in its ... growth in demand has driven several recent investments. ... 2001 it had one filling line with small-scale ...
(Date:2/11/2016)... Ore. , Feb. 11, 2016 Wellpartner, ... announce the acquisition of SolutionsRx, a full-service 340B company ... Along with providing traditional contract pharmacy services, SolutionsRx also ... clients in navigating the complex 340B regulatory environment. ... --> James R. Love , CEO of ...
Breaking Medicine Technology: