Leptin and Adiponectin: new players in the field of tumor cell and leukocyte migration.

Adipose tissue is no longer considered to be solely an energy storage, but exerts important endocrine functions, which are primarily mediated by a network of various soluble factors derived from fat cells, called adipocytokines. In addition to their responsibility to influence energy homeostasis, new studies have identified important pathways linking metabolism with the immune system, and demonstrating a modulatory role of adipocytokines in immune function. Additionally, epidemiological studies underline that obesity represents a significant risk factor for the development of cancer, although the exact mechanism of this relationship remains to be determined. Whereas a possible influence of adipocytokines on the proliferation of tumor cells is already known, new evidence has come to light elucidating a modulatory role of this signaling substances in the regulation of migration of leukocytes and tumor cells. The migration of leukocytes is a key feature to fight cancer cells, whereas the locomotion of tumor cells is a prerequisite for tumor formation and metastasis. We herein review the latest tumor biological findings on the role of the most prominent adipocytokines leptin and adiponectin, which are secreted by fat cells, and which are involved in leukocyte migration, tumor growth, invasion and metastasis. This review thus accentuates the complex, interactive involvement of adipocytokines in the regulation of migration of both leukocytes and tumor cells, and gives an insight in the underlying molecular mechanisms.

Leptin stimulates the migration of colon carcinoma cells by multiple signaling pathways.

Active migration of tumor cells is a prerequisite for the development of metastasis and tumor progression, and is regulated by a variety of extracellular ligands. Epidemiological studies have shown that obesity increases the risk of colon cancer by 1.5- to 2-fold with obesity-associated colon cancer accounting for 14-35% of total incidence. In obese individuals, serum levels of leptin are markedly increased, and therefore, we have investigated the impact of this adipocytokine on the migration of various human colon carcinoma cell lines such as SW480, SW620, and HCT116. Leptin significantly enhanced the migratory activity of all three cell lines, and the strongest effect was observed in SW480 cells, which increased their locomotor activity from 28% spontaneously locomoting cells to 50%. The intracellular signal transduction regulating this pro-migratory effect involves the activation of the transcription factor signal transducer and activator of transcription-3 via Janus kinases, but also the activity of src tyrosine kinases, focal adhesion kinase, exclusively protein kinase Cdelta, and the phosphatidyl-inositol-3-kinase, as proven by the use of particular inhibitors and target-specific small interfering RNAs. Herein, we deliver new evidence for a modulatory role of leptin in the regulation of colon cancer progression by stimulating tumor cell migration. Thus, our findings have potential clinical implications, because understanding the impact of leptin on tumor cell migration and the underlying signal transduction mechanisms is mandatory for future development of novel therapeutics to treat obesity-associated colorectal cancer.

Pitt, a novel tetratricopeptide repeat protein involved in light-dependent chlorophyll biosynthesis and thylakoid membrane biogenesis in Synechocystis sp. PCC 6803.

Biogenesis of photosynthetic pigment/protein complexes is a highly regulated process that requires various assisting factors. Here, we report on the molecular analysis of the Pitt gene (slr1644) from the cyanobacterium Synechocystis sp. PCC 6803 (Synechocystis 6803) that encodes a membrane-bound tetratricopeptide repeat (TPR) protein of formerly unknown function. Targeted inactivation of Pitt affected photosynthetic performance and light-dependent chlorophyll synthesis. Yeast two-hybrid analyses and native PAGE strongly suggest a complex formation between Pitt and the light-dependent protochlorophyllide oxidoreductase (POR). Consistently, POR levels are approximately threefold reduced in the pitt insertion mutant. The membrane sublocalization of Pitt was found to be dependent on the presence of the periplasmic photosystem II (PSII) biogenesis factor PratA, supporting the idea that Pitt is involved in the early steps of photosynthetic pigment/protein complex formation.