Palmitoylated claudin7 captured in glycolipid-enriched membrane microdomains promotes metastasis via associated transmembrane and cytosolic molecules.

In epithelial cells claudin7 (cld7) is a major component of tight junctions, but is also recovered from glycolipid-enriched membrane microdomains (GEM). In tumor cells, too, cld7 exists in two stages. Only GEM-located cld7, which is palmitoylated, promotes metastasis.

The importance of claudin-7 palmitoylation on membrane subdomain localization and metastasis-promoting activities.

Background: Claudin-7 (cld7), a tight junction (TJ) component, is also found basolaterally and in the cytoplasm. Basolaterally located cld7 is enriched in glycolipid-enriched membrane domains (GEM), where it associates with EpCAM (EpC). The conditions driving cld7 out of TJ into GEM, which is associated with a striking change in function, were not defined.

Claudin-7 promotes the epithelial-mesenchymal transition in human colorectal cancer.

In colorectal cancer (CoCa) EpCAM is frequently associated with claudin-7. There is evidence that tumor-promoting EpCAM activities are modulated by the association with claudin-7. To support this hypothesis, claudin-7 was knocked-down (kd) in HT29 and SW948 cells.

Outsmart tumor exosomes to steal the cancer initiating cell its niche.

Exosomes are small vesicles that derive from endosomes and are delivered by many cells, including tumor cells that are a particular rich source of exosomes. Exosomes are suggested to be the most potent intercellular communicators. Being recovered in all body fluids, they can communicate with neighboring as well as distant cells.

The metastasis-associated molecule C4.4A promotes tissue invasion and anchorage independence by associating with the alpha6beta4 integrin.

C4.4A is a metastasis-associated molecule that functions appear to rely on associated alph6beta4 integrin. To corroborate the impact of the C4.

EpCAM-associated claudin-7 supports lymphatic spread and drug resistance in rat pancreatic cancer.

Pancreatic cancer has a dismal prognosis because of early metastatic spread, a suggested feature of cancer-initiating cells (CIC). To control for a functional contribution of the pancreatic CIC-marker EpCAM, we explored metastasis formation by a stable EpCAM-knockdown (ASML-EpC(kd)) of the rat pancreatic adenocarcinoma line BSp73ASML (ASML(wt)). As EpCAM associates with claudin-7, an ASML-claudin-7-knockdown (ASML-cld7(kd)) was included to differentiate between EpC- and EpC-cld7-mediated effects.

ROCK signaling mediates the adoption of different modes of migration and invasion in human mammary epithelial tumor cells.

For the invasive migration of tumor cells, at least two mechanisms are currently discussed: (1) the mesenchymal mode depending on extracellular proteolysis and (2) the proteolysis-independent amoeboid mode depending on the activity of the Rho kinase ROCK. The ability of tumor cells to switch between different modes of motility has been shown to limit the efficiency of agents aimed to reduce invasion. Here we show by combining 2D and 3D migration assays that human mammary tumor cells exhibited a strongly reduced migration velocity as compared to their normal counterparts indicating that high invasiveness is not necessarily correlated with high migratory capacity in 2D assays.