GLO 1 and PKCλ Regulate ALDH1-positive Breast Cancer Stem Cell Survival

Motomura, Hitomi; Tamori, Shoma; Yatani, Masa-Aki; Namiki, Ayano; Onaga, Chotaro; Ozaki, Ayaka; Takasawa, Ryoko; Mano, Yasunari; Sato, Tsugumichi; Hara, Yasushi; Sato, Keiko; Xiong, Yuyun; Harada, Yohsuke; Hanawa, Takehisa; Tanuma, Sei–ichi; Sasaki, Kazunori; Ohno, Shigeo; Akimoto, Kazunori

doi:10.21873/anticanres.15415

Cited by 10 publications

(10 citation statements)

References 40 publications

(100 reference statements)

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“…Western blotting. Western blotting of cells was performed as previously described (60,(66)(67)(68)(69)(70). The following antibodies were used: Rabbit polyclonal anti-p62 (PM045, 1:10000; Medical & Biological Laboratories, Tokyo, Japan); mouse monoclonal anti-p62 (610833, 1:10,000; BD Biosciences, San Jose, CA, USA); rabbit monoclonal anti-ALDH1A1 (ab52492, 1:3,000; Abcam, Cambridge, UK); rabbit polyclonal anti-ALDH1A3 (PA5-29188, 1:5,000; Thermo Fisher Scientific, Inc.); mouse monoclonal anti-β-actin (60008-I-Ig, 1:10,000; ProteinTech Group, Inc., Rosemont, IL, USA) as the primary antibodies.…”

Section: Analysis Of the Molecular Taxonomy Of Breast Cancer Internat...mentioning

confidence: 99%

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High Expression of p62 and ALDH1A3 Is Associated With Poor Prognosis in Luminal B Breast Cancer

et al. 2022

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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

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Section: Analysis Of the Molecular Taxonomy Of Breast Cancer Internat...mentioning

confidence: 99%

“…Tumor-sphere culture. Tumor-sphere formation assay was conducted as previously described (60,(66)(67)(68)(69)(70)(71). ALDH1 high cells were isolated via ALDEFLUOR assay upon p62 KD.…”

Section: Analysis Of the Molecular Taxonomy Of Breast Cancer Internat...mentioning

confidence: 99%

High Expression of p62 and ALDH1A3 Is Associated With Poor Prognosis in Luminal B Breast Cancer

et al. 2022

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“…Western blot analysis. Western blot analysis was performed as previously described (9)(10)(11)(12)(13)15). Anti-CD58 (LFA-3) antibody (330902) was obtained from BioLegend, Inc. (San Diego, CA, USA) and was diluted to 1:1,000.…”

Section: Analysis Of the Molecular Taxonomy Of Breast Cancer Internat...mentioning

confidence: 99%

“…The ALDEFLUOR™ assay kit was obtained from Stemcell Technologies, Inc. (Vancouver, BC, Canada). Following transfection, ALDH1 high cells were sorted from MDA-MB-468 and BT-20 cells using the ALDEFLUOR™ assay kit as previously described (8,9,(11)(12)(13)15). Cells were sorted using a FACS Aria III cell sorter (BD Biosciences, San Jose, CA, USA).…”

Section: Analysis Of the Molecular Taxonomy Of Breast Cancer Internat...mentioning

confidence: 99%

“…an urgent need for the development of effective biomarkers for prognosis and treatment targets for diverse individual tumours of different subtypes. We have previously published a series of articles in recent years and screened a number of genes playing a key role in the diagnosis, prognosis, and therapy for each subtype of breast cancer (7)(8)(9)(10)(11)(12)(13)(14)(15). Hence, the present study continued the search for characteristic genes and the identification of explicit gene functions among different subtypes in breast cancer.…”

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High Expression ofCD58andALDH1A3Predicts a Poor Prognosis in Basal-like Breast Cancer

Xiong¹,

Motomura²,

Tamori³

et al. 2022

Anticancer Res

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Background/Aim: CD58 is an immune adhesion molecule on the cellular surface. It was previously found that a high expression of CD58 predicted a poor prognosis of patients with lower-grade gliomas. Therefore, the aim of this paper was to investigate the association between CD58 and breast cancer. Materials and Methods: CD58 gene expression data downloaded from cBioPortal was compared between the different subtypes of breast cancer. Clinical prognosis was examined using Kaplan-Meier analysis and multivariable Cox regression analysis. The association between CD58 expression and immune cell infiltration was estimated using the TIMER 2.0 web platform. Finally, the tumour sphere formation of aldehyde dehydrogenase 1 (ALDH1) high basallike breast cancer stem cells in which CD58 was knocked down using siRNA was measured. Results: CD58 mRNA was mainly enriched in claudin-low and basal-like subtypes. The high expression of CD58 predicted a good prognosis in patients with luminal A and luminal B breast cancer. This prediction may be due to the association of immune cell infiltration with CD58. Notably, patients with luminal A breast cancer with a high expression of CD58 in association with ALDH1A3 exhibited a good prognosis; however, this did not apply to patients with basal-like breast cancer. The in vitro experiments revealed that knockdown of CD58 inhibited the tumour sphere formation ability of ALDH1 high basal-like cancer cells. Conclusion: CD58 may function as a potential prognostic biomarker and therapeutic target in ALDHpositive basal-like cancer stem cells.According to the enumeration published in 2022, over 287,000 new cases of breast cancer have been estimated to be diagnosed in the United States each year, with breast cancer accounting for 31% of all cancers among females. In addition, over 43,000 women are estimated to succumb to the disease each year (1). Breast cancer is a heterogeneous disease which can be subtyped by predictive analysis of the microarrays 50 (PAM50) gene panel. Breast cancer PAM50 molecular subtypes include luminal A, luminal B, human epidermal growth factor receptor 2 (HER2)-enriched, basallike, normal-like and claudin-low. Luminal A and B subtypes are mainly associated with oestrogen receptor (ER) + cancers (2, 3), while the majority of triple-negative breast cancers (TNBCs) are also classified as claudin-low and basal-like subtypes (4).Based on the subtyping, treatment of breast cancer mainly entails surgery, radiotherapy, and drug therapy, including chemotherapy, endocrine therapy and molecular targeted therapy. In general, patients with luminal A breast cancer have a favourable prognosis owing to the effectiveness of anti-hormone receptor therapy (5). By contrast, patients with the basal-like subtype have an unfavourable prognosis due to resistance to conventional therapy (6). Therefore, there is 5223

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High expression of PKCλ and ALDH1A3 indicates a poor prognosis, and PKCλ is required for the asymmetric cell division of ALDH1A3-positive cancer stem cells in PDAC

Kasai

Tamori

Takasaki

et al. 2023

Biochemical and Biophysical Research Communications

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GLO 1 and PKCλ Regulate ALDH1-positive Breast Cancer Stem Cell Survival

Cited by 10 publications

References 40 publications

High Expression of p62 and ALDH1A3 Is Associated With Poor Prognosis in Luminal B Breast Cancer

High Expression of p62 and ALDH1A3 Is Associated With Poor Prognosis in Luminal B Breast Cancer

High Expression ofCD58andALDH1A3Predicts a Poor Prognosis in Basal-like Breast Cancer

High expression of PKCλ and ALDH1A3 indicates a poor prognosis, and PKCλ is required for the asymmetric cell division of ALDH1A3-positive cancer stem cells in PDAC

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