Yuksel UM, etal., Oncol Res Treat. 2015;38(9):431-4. doi: 10.1159/000438501. Epub 2015 Aug 10.
BACKGROUND: CSE1L (chromosome segregation 1-like) is the human homologue to the yeast gene CSE1, and is related to invasion and metastasis in cancer progression. The aim of this study was to investigate the potential role of CSE1L
/span> expression in distant metastasis of breast cancer. PATIENTS AND METHODS: A total of 71 breast cancer patients were included in this study. Clinical characteristics and CSE1L status were evaluated. Immunohistochemistry was performed on formalin-fixed, paraffin-embedded archival breast tumor tissue. The results of CSE1L staining were analyzed according to the percentage of immunoreactive cells. RESULTS: 34 patients had distant metastasis and 37 did not. The mean age of the patients was 50.5 +/- 12.1 years. Age, tumor size, and hormone receptor status were similar in patients with distant metastasis and in those without. A statistically significant relationship was found between nuclear CSE1L expression and distant metastasis of breast cancer. Lymph node metastasis and nuclear grade were other factors affecting distant metastasis. CONCLUSION: There is a relationship between nuclear CSE1L overexpression and distant metastasis in breast cancer. CSE1L status may therefore become a valuable prognostic tool in the future.
Homologous recombinational repair (HR) is one of the major repair systems for DNA double-strand breaks. RAD51 is a key molecule in HR, and the RAD51 concentration in the cell nucleus increases after DNA damage induction. However, the mechanism that regulates the intracellular distribution of RAD51
is still unclear. Here, we show that hCAS/CSE1L associates with RAD51 in human cells. We found that hCAS/CSE1L negatively regulates the nuclear protein level of RAD51 under normal conditions. hCAS/CSE1L is also required to repress the DNA damage-induced focus formation of RAD51. Moreover, we show that hCAS/CSE1L plays roles in the regulation of the HR activity and in chromosome stability. These findings suggest that hCAS/CSE1L is responsible for controlling the HR activity by directly interacting with RAD51.
Lee WR, etal., J Transl Med. 2015 Jun 13;13:191. doi: 10.1186/s12967-015-0553-6.
BACKGROUND: Although targeted therapies have improved the clinical outcomes of cancer treatment, tumors resistance to targeted drug are often detected too late and cause mortality. CSE1L is secreted from tumor and its phosphorylation is regulated by ERK1/2. ERK
1/2 is located downstream of various growth factor receptors and kinases, the targets of most targeted drugs. Serum phospho-CSE1L may be a marker for monitoring the efficacy of targeted therapy. METHODS: We used mice tumor xenograft model to study the assay of serum phosphorylated CSE1L for early detecting the efficacy of targeted drugs. The phosphorylation status of CSE1L in vemurafenib and sorafenib treated tumor cells were assayed by immunoblotting with antibody against phosphorylated CSE1L. RESULTS: Ras activation increased phospho-CSE1L expression in B16F10 melanoma cells. Vemurafenib and sorafenib treatment did not significantly reduce the total CSE1L levels; however, they inhibited ERK1/2 and CSE1L phosphorylation in A375 melanoma cells and HT-29 colorectal cancer cells. In the melanoma xenograft model, serum phospho-CSE1L level declined 5 days after vemurafenib/sunitinib treatment and 3 days after sorafenib/lapatinib treatment in the HT-29 colon cancer xenograft model. Vemurafenib/sunitinib and sorafenib/lapatinib treatments resulted in tumor regression. CONCLUSIONS: Our results indicated that serum phospho-CSE1L is useful for early detecting the efficacy of targeted therapy in initial treatment and for monitoring emerging secondary drug resistance to facilitate timely therapeutic decision making.