Depletion of the actin bundling protein SM22/transgelin increases actin dynamics and enhances the tumourigenic phenotypes of cells

Background SM22 has long been studied as an actin-associated protein. Interestingly, levels of SM22 are often reduced in tumour cell lines, while they are increased during senescence possibly indicating a role for SM22 in cell fate decisions via its interaction with actin. In this study we aimed to determine whether reducing levels of SM22 could actively contribute to a tumourigenic phenotype. Results We demonstrate that in REF52 fibroblasts, decreased levels of SM22 disrupt normal actin organization leading to changes in the motile behaviour of cells. Interestingly, SM22 depletion also led to an increase in the capacity of cells to spontaneously form podosomes with a concomitant increase in the ability to invade Matrigel. In PC3 prostate epithelial cancer cells by contrast, where SM22 is undetectable, re-expression of SM22 reduced the ability to invade Matrigel. Furthermore SM22 depleted cells also had reduced levels of reactive oxygen species when under serum starvation stress. Conclusions These findings suggest that depletion of SM22 could contribute to tumourigenic properties of cells. Reduction in SM22 levels would tend to promote cell survival when cells are under stress, such as in a hypoxic tumour environment, and may also contribute to increases in actin dynamics that favour metastatic potential

Clinicopathologic features and prognosis of triple-negative breast cancer in patients 40 years of age and younger in Saudi Arabia

BACKGROUND AND OBJECTIVES: Triple-negative breast cancer (TNBC) has a poor prognosis and overall survival (os) compared to other types of breast cancer tumors. however, there is to date no evidence that this is also the case in saudi Arabia. DESIGN AND SETTING: Retrospective review of breast cancer patients who were treated from January 2001 to December 2008 (517 patients) at the King AbdulAziz Medical City, riyadh, saudi Arabia. PATIENTS AND METHODS: Patients were selected as TNBC if all three markers of estrogen receptor (ER), progesterone receptor (PR) and the human epidermal growth factor (HER2) tested by immunohistochemistry as negative. They were then age- and stage-matched, and compared with non-TNBC patients to examine differences, if any, in their clinicopathologic features, prognosis and OS. RESULTS: Twenty-six patients with a follow up time of at least three years were identified as TNBC. Thirty-three patients who were age- and stage-matched were selected as the non-TnBC controls. Clinicopathologic results illustrated significantly more grade 3 tumors (P=.02) and CK 5/6 expression (P40 years (P=.01), and when compared to the non-TnBC group (P=.04). CONCLUSION: The incidence of TNBC in our cohort is similar to what has been illustrated in previous studies in Western population. There was no significant difference in 3-year survival between TNBC and non-TnBC groups. however, the aggressiveness of this type of tumor and os is significantly higher in younger patients aged <40 years, compared to those over 40 years of age

Characterization of a Novel Human SMC Heterodimer Homologous to the Schizosaccharomyces pombe Rad18/Spr18 Complex

The structural maintenance of chromosomes (SMC) protein encoded by the fission yeast rad18 gene is involved in several DNA repair processes and has an essential function in DNA replication and mitotic control. It has a heterodimeric partner SMC protein, Spr18, with which it forms the core of a multiprotein complex. We have now isolated the human orthologues of rad18 and spr18 and designated them hSMC6 and hSMC5. Both proteins are about 1100 amino acids in length and are 27–28% identical to their fission yeast orthologues, with much greater identity within their N- and C-terminal globular domains. The hSMC6 and hSMC5 proteins interact to form a tight complex analogous to the yeast Rad18/Spr18 heterodimer. In proliferating human cells the proteins are bound to both chromatin and the nucleoskeleton. In addition, we have detected a phosphorylated form of hSMC6 that localizes to interchromatin granule clusters. Both the total level of hSMC6 and its phosphorylated form remain constant through the cell cycle. Both hSMC5 and hSMC6 proteins are expressed at extremely high levels in the testis and associate with the sex chromosomes in the late stages of meiotic prophase, suggesting a possible role for these proteins in meiosis