metastasis

MicroRNAs Suppress Cancer Metastasis

by Chris on January 26, 2011

Prostate Cancer

microRNA inhibits prostate cancer metastasis by suppressing a surface protein (CD44) commonly found on prostate cancer stem cells. A research team led by scientists at The University of Texas MD Anderson Cancer Center reported in an advance online publication at Nature Medicine1.

The researchers demonstrated that miR-34a inhibits prostate cancer stem cells by suppressing CD44 and most significantly, that intravenous treatment of tumor-bearing mice with synthetic miR-34a reduced tumor burden by half in one tumor type. It also steeply reduced lung metastases in another tumor type, resulting in increased animal survival.

Breast Cancer

In a previous groundbreaking study, researchers at Memorial Sloan-Kettering Cancer Center found a specific set of microRNAs for which expression is specifically lost as human breast cancer cells develop metastatic potential2. Furthermore, they show that restoring the expression of these microRNAs in malignant cells reduces overall tumor growth and proliferation and suppresses metastatic cell invasion.

1.     Liu C, Kelnar K, Liu B, Chen X, Calhoun-Davis T, Li H, Patrawala L, Yan H, Jeter C, Honorio S, Wiggins JF, Bader AG, Fagin R, Brown D, Tang DG. (2011) The microRNA miR-34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44. Nat Med [Epub ahead of print]. [abstract]

2.     Tavazoie SF, Alarcón C, Oskarsson T, Padua D, Wang Q, Bos PD, Gerald WL, Massagué J. (2008) Endogenous human microRNAs that suppress breast cancer metastasis. Nature 451(7175), 147-52.  [abstract]

MDACC News Release 1/16/11

MSKCC News Release 1/9/08

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Featured Publication – miR-661 expression in SNAI1-induced epithelial to mesenchymal transition contributes to breast cancer cell invasion by targeting Nectin-1 and StarD10 messengers

by Chris on June 24, 2010

Epithelial to mesenchymal transition (EMT) is a key step toward metastasis. MCF7 breast cancer cells conditionally expressing the EMT master regulator SNAI1 were used to identify early expressed microRNAs (miRNAs) and their targets that may contribute to the EMT process. Potential targets of miRNAs were identified by matching lists of in silico predicted targets and of inversely expressed mRNAs. MiRNAs were ranked based on the number of predicted hits, highlighting miR-661, a miRNA with so far no reported role in EMT. MiR-661 was found required for efficient invasion of breast cancer cells by destabilizing two of its predicted mRNA targets, the cell–cell adhesion protein Nectin-1 and the lipid transferase StarD10, resulting, in turn, in the downregulation of epithelial markers. [click to continue…]

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microRNA of the Week: microRNA-200 Family

by Chris on March 26, 2010

The miR-200 family is a particularly nasty group of microRNAs. Changes in miR-200 family levels have been associated with enhanced tumorigenesis and significantly correlated with decreased survival. 

miR-200 family members are associated with resistance to several chemotherapy drugs: docetaxel  in non-small cell cancer cells1, cisplatin in breast cancer cells2, and gemcitabine in cholangiocarcinoma cells.

It has been shown that many microRNAs play an important role in regulating metastasis, the ultimate cause of death of most cancer patients, and in particular, miR-200 is responsible for direct enhancement of distant metastases of breast cancer3.

Additionally miR-200 family members are significantly over-expressed in human ovarian cancer4 and likewise are a factor in the etiology of endometriosis5.

  1. Rui W, Bing F, Hai-Zhu S, Wei D, Long-Bang C.  (2009)  Identification of microRNA profiles in docetaxel-resistant human non-small cell lung carcinoma cells (SPC-A1).  J Cell Mol Med [Epub ahead of print]  [abstract]
  2. Pogribny IP, Filkowski JN, Tryndyak VP, Golubov A, Shpyleva SI, Kovalchuk O. (2010) Alterations of microRNAs and their targets are associated with acquired resistance of MCF-7 breast cancer cells to cisplatin. Int J Cancer [Epub ahead of print] [abstract]
  3. Dykxhoorn DM, Wu Y, Xie H, Yu F, Lal A, Petrocca F, Martinvalet D, Song E, Lim B, Lieberman J.  (2009) miR-200 enhances mouse breast cancer cell colonization to form distant metastases.  PLoS One 4(9), e7181.  [abstract]
  4. Iorio MV, Visone R, Di Leva G, Donati V, Petrocca F, Casalini P, Taccioli C, Volinia S, Liu CG, Alder H, Calin GA, Ménard S, Croce CM. (2007) MicroRNA signatures in human ovarian cancer. Cancer Res 67(18), 8699-707. [abstract]
  5. Filigheddu N, Gregnanin I, Porporato PE, Surico D, Perego B, Galli L, Patrignani C, Graziani A, Surico N. Differential expression of microRNAs between eutopic and ectopic endometrium in ovarian endometriosis. J Biomed Biotechnol 2010:369549. [abstract]

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