Background/Aim: p62 (also known as sequestosome 1) is involved in cancer progression, and high expression of p62 indicates poor clinical outcome in several cancer types. However, the association between p62 gene expression and cancer stem cells (CSCs) in breast cancer subtypes remains unclear. Materials and Methods: In the present study, genomic datasets of primary breast cancer (The Cancer Genome Atlas, n=593; and Molecular Taxonomy of Breast Cancer International Consortium, n=2,509) were downloaded. p62 Expression was then examined in normal and breast cancer tissues derived from the same patients. Kaplan-Meier and multivariate Cox regression analyses were employed to evaluate disease-specific survival. Next, the effect on cell viability and in vitro tumor-sphere formation of p62 knockdown using targeted small interfering RNA was assessed by using cells with high activity of aldehyde dehydrogenase 1 (ALDH1 high ). Results: Patients with normal-like, luminal A or luminal B breast cancer with p62 high had poor prognosis. Furthermore, patients with p62 high ALDH1A3 high luminal B type also exhibited poor prognoses. Knockdown of p62 suppressed viability and tumor-sphere formation by ALDH1 high cells of the luminal B-type cell lines BT-474 and MDA-MB- These results suggest that p62 is essential for cancerous progression of ALDH1-positive luminal B breast CSCs, and contributes to poor prognosis of luminal B breast cancer. Conclusion: p62 is potentially a prognostic marker and therapeutic target for ALDH1-positive luminal B breast CSCs.Breast cancer has the highest prevalence among cancers of women worldwide, with 2.26 million new cases (24.5% of all cancer cases in women) and 685,000 cancer-associated mortalities (15.5% of all cancer-associated mortalities among women) annually (1). Breast cancer is classified using two parameters: Immunohistochemistry and gene-expression patterns [prediction analysis of microarray 50 (PAM50)] (2-8). Based on its PAM50, breast cancer is classified into at least six subtypes: Normal-like, luminal A, luminal B, human epidermal growth factor receptor type 2 (HER2)-enriched, claudin-low and basal-like (5, 7, 8). Among these, the luminal B type expresses estrogen receptor, and certain luminal B tumors express HER2 and highly express proliferation-related genes such as marker of proliferation Ki-67 (MKI67). In addition, the luminal B type has poorer prognosis (7,(9)(10)(11)(12)(13)(14)(15). Breast cancer treatment mainly entails surgery, radiotherapy and drug therapy, including chemotherapy, endocrine therapy and molecular targeted therapy. However, there are still numerous 3299

Chloramphenicol (Cm) is a broad-spectrum classic antibiotic active against prokaryotic organisms. However, Cm has severe side effects in eukaryotes of which the cause remains unknown. The plant pathogenic fungus Magnaporthe oryzae , which causes rice blast, forms an appressorium to infect the host cell via single-cell differentiation. Chloramphenicol specifically inhibits appressorium formation, which indicates that Cm has a novel molecular target (or targets) in the rice blast fungus. Application of the T7 phage display method inferred that MoDullard, a Ser/Thr-protein phosphatase, may be a target of Cm. In animals Dullard functions in cell differentiation and protein synthesis, but in fungi its role is poorly understood. In vivo and in vitro analyses showed that MoDullard is required for appressorium formation, and that Cm can bind to and inhibit MoDullard function. Given that human phosphatase CTDSP1 complemented the MoDullard function during appressorium formation by M. oryzae , CTDSP1 may be a novel molecular target of Cm in eukaryotes.

Roxithromycin (RXM), active against prokaryotes, has beneficial side effects such as anti-cancer activities on mammalian cells, but the mechanisms underlying these effects remain unclear. We found that RXM inhibited the cellular differentiation of the rice blast fungus Magnaporthe oryzae. Hence, we screened the targets of RXM by the T7 phage display method with fungal genomic DNA, and identified MoCDC27 (M. oryzae Cell Division Cycle 27) as a candidate. We generated mocdc27 knockdown mutants that the appressoria formation was less affected by RXM. A complemented mutant restored sensitivity against RXM to the level of the wild type. These results suggest that MoCDC27 was involved in the inhibition of appressorium formation by RXM, and that the complex of RXM-MoCDC27 affected another molecule involved in appressorium formation. The T7 phage display method with fungal genomic DNA can be a useful tool in the quest for drug target.

Estrogen receptor-positive (ER+) breast cancer intrinsically confers satisfactory clinical outcomes in response to endocrine therapy. However, a significant proportion of patients with ER+ breast cancer do not respond well to this treatment. Therefore, to evaluate the effects of endocrine therapy, there is a need for identification of novel markers that can be used at the time of diagnosis for predicting clinical outcomes, especially for early-stage and late recurrence. Solute carrier family 20 member 1 (SLC20A1) is a sodium/inorganic phosphate symporter that has been proposed to be a viable prognostic marker for the luminal A and luminal B types of ER+ breast cancer. In the present study, we examined the possible association of SLC20A1 expression with tumor staging, endocrine therapy and chemotherapy in the luminal A and luminal B subtypes of breast cancer. In addition, we analyzed the relationship between SLC20A1 expression and late recurrence in patients with luminal A and luminal B breast cancer following endocrine therapy. We showed that patients with higher levels of SLC20A1 expression (SLC20A1high) exhibited poorer clinical outcomes in those with tumor stage I luminal A breast cancer. In addition, this SLC20A1high subgroup of patients exhibited less responses to endocrine therapy, specifically in those with the luminal A and luminal B subtypes of breast cancer. However, patients with SLC20A1high showed good clinical outcomes following chemotherapy. Patients tested to be in the SLC20A1high group at the time of diagnosis also showed a higher incidence of recurrence compared with those with lower expression levels of SLC20A1, at >15 years for luminal A breast cancer and at 10–15 years for luminal B breast cancer. Therefore, we conclude that SLC20A1high can be used as a prognostic biomarker for predicting the efficacy of endocrine therapy and late recurrence for ER+ breast cancer.

Background/Aim: Radiotherapy is one of the main treatments for estrogen receptor-positive (ER+) breast cancer. However, in some ER+ breast cancer cases, radiotherapy is insufficient to inhibit progression and there is a lack of markers to predict radiotherapy insensitivity. Solute carrier family 20 member 1 (SLC20A1) is a sodium/inorganic phosphate symporter, which has been proposed to be a viable prognostic marker for luminal A and B types of ER+ breast cancer. The present study examined the possibility of SLC20A1 as a novel biomarker for the prediction of radiotherapy efficiency. Patients and Methods: The Molecular Taxonomy of Breast Cancer International Consortium dataset was downloaded from cBioportal and the prognosis of patients with high SLC20A1 expression (SLC20A1high) was compared with that of patients with low SLC20A1 expression, without or with radiotherapy and tumor stages I, II, and III, using the Kaplan–Meier method and multivariate Cox regression analyses of disease-specific and relapse-free survival. Results: Patients in the SLC20A1high group with radiotherapy showed poor clinical outcomes in both luminal A and luminal B breast cancers. Furthermore, in luminal A breast cancer at tumor stage I, patients in the SLC20A1high group with radiotherapy also showed poor clinical outcomes. Therefore, these results suggest that radiotherapy is insufficient for patients in the SLC20A1high group for both luminal A and B types, and especially for the luminal A type at tumor stage I. Conclusion: SLC20A1 can be used as a prognostic marker for the prediction of the efficacy of radiotherapy for luminal A and luminal B breast cancers.