WNT4 antibody detects WNT4 protein by western blot analysis. Non-transfected (-) and Wnt4-transfected (+, including V5-tag) 293T whole cell extracts (100 μg) were separated by 10% SDS-PAGE, and the membrane was blotted with WNT4 antibody (Cat. No. 210GTX101085) at a dilution of 1:2500. The V5 was used as internal control (Cat. No. 210GTX117997, 1:2500) shown at the bottom panel.

The behavior of adult mammary stem cells (MaSCs) is precisely controlled by the activities of hormones and local factors, though the underlying mechanisms remain obscure. A recent report by Cai et al in Genes & Development illustrates the dynamic interaction between systemic ovarian hormones, Wnt signaling, and the Wnt agonist R-spondin1 (Rspo1) to promote MaSC self-renewal.

In response to estradiol and progesterone, R-spondin1 and Wnt4, but not Wnt7B, act as niche factors to drive MaSC regeneration, with Wnt4 acting through the canonical Wnt/β-catenin signaling pathway. This work establishes a clear mechanistic link between locally acting Wnt signals and the systemic hormone growth response of MaSCs, unveiling the intriguing concept that hormones induce a collaborative local niche environment for stem cells.

Working on unveiling the mechanisms of stem cell fate and differentiation? We’d like to hear from you!

PARPs (Poly ADP ribose polymerases) are found in the nucleus of the cell and they are involved in SSB repair (single-strand DNA breaks). PARP is known to bind damaged DNA through its N-terminal zinc finger domain. Subsequently it starts to synthesize a poly (ADP-ribose) chain which serves as a signal for other DNA-repairing enzymes.

Fig. 1: Principle of synthetic lethality

PARP inhibitors are considered to be promising  candidates as anti cancer drugs (recently Olaparib, the first drug directed against PARP1, has been approved by the European commission). One of the reasons is that some tumors are more dependent on PARP than regular cells. These cancer cells are mutated in BRCA1 or BRCA2 – both genes which are involved in key DNA damage repair mechanisms. In healthy cells PARPs can function as a kind of back-up system and let the cells survive even without functional BRCA gene products. When PARPs are inhibited the cells do not possess any functional SSB repair mechanism anymore and are bound to die (Fig. 1; take a look at PARPs as cancer drug targets – first EC-approved drug to learn more about the concept of “synthetic lethality”).

The transition from non-invasive phenotype to invasive phenotype of tumor cells marks the switch from a benign tumor to a more malignant form of cancer. Understanding the mechanisms underlying this hallmark event, which enables tumor cells to invade through Extracellular matrix, is critical for discovering pathways and new targets to develop anti-metastatic strategies. In a previous post, A 96-well Invasion Assay Compatible with High Content Screening, I introduced a technology called Oris™ assays, which employs exclusion zone technology to facilitate unambiguous monitoring of cell migration from the periphery into a central circular detection zone. This assay is a high-throughput assay, but compatible with adherent cells only.  Today I’d like to introduce a new 3D Embedded Invasion Assay, compatible with both non-adherent and adherent cells.