Go J Yoshida

Go J Yoshida
Juntendo University · Department of Pathology and Oncology

M.D., Ph.D.

About

52
Publications
191,972
Reads
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1,908
Citations
Introduction
1: To elucidate the function of cancer stem cell markers; CD44 and EpCAM, in the perspective of redox stress regulation and susceptibility to nutrient/growth factor microenvironment 2: To identify the stemness of melanocytic progenitor cells in eccrine glands and the contribution of McSCs (melanocytic stem cells) to the development of acral melanoma with gene-engineering mouse model
Additional affiliations
April 2018 - present
Juntendo University
Position
  • Professor (Assistant)
April 2015 - March 2018
Tokyo Medical and Dental University
Position
  • JSPS Postdoctoral Fellow
April 2015 - March 2018
Japan Society for the Promotion of Science
Position
  • PostDoc Position
Education
April 2004 - March 2010
School of Medicine, Keio University, Tokyo, Japan
Field of study
  • Basic and Clinical Medicine

Publications

Publications (52)
Article
Cancer stem-like cells express high amount of CD44 variant8-10 which protects cancer cells from redox stress. We have demonstrated by immunohistochemical analysis and Western blotting, and reverse-transcription polymerase chain reaction, that CD44 variant8-10 and c-Myc tend to show the inversed expression manner in gastric cancer cells. That is att...
Article
Full-text available
Tumor tissue is composed of cancer cells and surrounding stromal cells with diverse genetic/epigenetic backgrounds, a situation known as intra-tumoral heterogeneity. Cancer cells are surrounded by a totally different microenvironment than that of normal cells; consequently, tumor cells must exhibit rapidly adaptive responses to hypoxia and hypo-nut...
Article
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Cancer stem cells (CSCs) are undifferentiated cancer cells with a high tumorigenic activity, the ability to undergo self-renewal, and a multi-lineage differentiation potential. CSCs are responsible for the development of tumor cell heterogeneity, a key feature for resistance to anticancer treatments including conventional chemotherapy, radiation th...
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Intratumoral heterogeneity is tightly associated with the failure of anticancer treatment modalities including conventional chemotherapy, radiation therapy, and molecularly targeted therapy. Such heterogeneity is generated in an evolutionary manner not only as a result of genetic alterations but also by the presence of cancer stem cells (CSCs). CSC...
Article
The concept of a “cancer stem cell” has evolved over the past decades, and research on cancer stem cell biology has entered into a stage of remarkable progress. Cancer stem cells are a major determining factor contributing to the establishment of phenotypic and functional intratumoral heterogeneity in synchronization with their surrounding “cancer...
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There is a growing body of evidence that metabolic reprogramming contributes to the acquisition and maintenance of robustness associated with malignancy. The fine regulation of expression levels of amino acid and monocarboxylate transporters enables cancer cells to exhibit the metabolic reprogramming that is responsible for therapeutic resistance....
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Accumulating evidence indicates that intratumoral heterogeneity contributes to the development of resistance to anticancer therapeutics. Fibroblasts, which are components of the paraneoplastic stroma, play a crucial role in the wound-healing process. Activated fibroblasts accumulate in the wound and are involved in many aspects of the tissue remode...
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In 2018, Schneider and Zouboulis analyzed the available tools for studying sebaceous gland pathophysiology in vitro. Since then, the interest in this field remains unbroken, as demonstrated by recent reviews on sebaceous gland physiology, endocrinology and neurobiology, the role of sebaceous glands beyond acne, and several original works on differe...
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Cancer cells generate large amounts of lactate derived from glucose regardless of the available oxygen level. Cancer cells finely control ATP synthesis by modulating the uptake of substrates and the activity of enzymes involved in aerobic glycolysis (Warburg effect), which enables them to adapt to the tumor microenvironment. However, increasing evi...
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Patient-derived tumor xenografts (PDXs), in which tumor fragments surgically dissected from cancer patients are directly transplanted into immunodeficient mice, have emerged as a useful model for translational research aimed at facilitating precision medicine. PDX susceptibility to anti-cancer drugs is closely correlated with clinical data in patie...
Conference Paper
There is a growing interest in the crosstalk between epithelial tumor cells and mesenchymal alpha-smooth muscle actin (alpha-SMA)-positive myofibroblasts, also referred to as cancer-associated fibroblasts (CAFs). Several machineries have been elucidated underlying CAFs which can promote tumorigenesis and impair drug sensitivity. CAFs also promote i...
Article
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We hypothesized that sorafenib plus transarterial chemoembolization (TACE) would confer survival benefits over sorafenib alone for advanced hepatocellular carcinoma (aHCC). We investigated this using the population-based All-Cancer Dataset to assemble a cohort (n=3,674; median age, 60; 83% men) of patients receiving sorafenib for aHCC (Child-Pugh A...
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Neoplastic epithelial cells coexist in carcinomas with various non-neoplastic stromal cells, together creating the tumor microenvironment. There is a growing interest in the cross-talk between tumor cells and stromal fibroblasts referred to as carcinoma-associated fibroblasts (CAFs), which are frequently present in human carcinomas. CAF populations...
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The pathophysiological roles and the therapeutic potentials of Myc family are reviewed in this article. The physiological functions and molecular machineries in stem cells, including embryonic stem (ES) cells and induced pluripotent stem (iPS) cells, are clearly described. The c-Myc/Max complex inhibits the ectopic differentiation of both types of...
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In the publication of this article [1] there are three errors.
Article
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The 2016 Nobel Prize in Physiology or Medicine was awarded to the researcher that discovered autophagy, which is an evolutionally conserved catabolic process which degrades cytoplasmic constituents and organelles in the lysosome. Autophagy plays a crucial role in both normal tissue homeostasis and tumor development and is necessary for cancer cells...
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Cancer stem-like cells exhibit the multi-functional roles to survive and persist for a long period in the minimal residual disease after the conventional anti-cancer treatments. Cancer stem-like cells of solid malignant tumors which highly express CD44v8-10, the variant isoform of CD44 generated by alternative splicing, has a resistance to redox st...
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Full-text available
Accumulating evidence suggests that the phenomenon of epithelial-mesenchymal-transition (EMT) plays a fundamental role in the tumor development. Several research articles have been published from Journal of Experimental and Clinical Cancer Research (JECCR) which have investigated into the molecular machineries underlying the importance of EMT for h...
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Apoptosis plays a pivotal role in development and tissue homeostasis in multicellular organisms. Clustering of Bak proteins on the mitochondrial outer membrane is responsible for the induction of apoptosis by evoking a release of pro-apoptotic proteins from mitochondria into cytosol. However, how the protein cluster permeabilizes the mitochondrial...
Article
To the Editor: Theoharides et al. (July 9 issue)(1) propose that underlying systemic mastocytosis should be considered in patients who have repeated episodes of anaphylaxis, even in the absence of clinical features of mast-cell hyperactivity. They also emphasize important triggers for anaphylaxis in such patients, including stings from insects of t...
Conference Paper
Accumulating evidence suggests that aquaporins (AQPs) play a crucial role not only in the normal tissue homeostasis but also in the aggressive phenotype of cancer cells. AQP-3, -7, -9 belong to the aquaglyceropolins, which permit the penetration of glycerol as well as water through the lipid cellular membrane. Firstly, IHC analysis reveals that AQP...
Article
Aquaporin-7 (AQP7) is expressed in adipose tissue, permeated by water and glycerol, and is involved in lipid metabolism. AQP7-null mice develop obesity, insulin resistance, and adipocyte hypertrophy. Here, we show that AQP7 is expressed in adipocyte plasma membranes, and is re-localized to intracellular membranes in response to catecholamine in mou...
Conference Paper
Full-text available
Determination of the origin of cancer remains a challenging issue. Human cutaneous melanoma is a highly aggressive cancer. The preferential proliferation of melanoma cells in the epidermis around sweat ducts is a reliable early diagnostic sign of acral melanoma that affects volar skin. Here, we report the identification of melanocyte stem cells (Mc...
Article
Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Cancer metastasis is established by the seeding and successful colonization of stem-like cancer cells which show tumor-initiating ability at distant organs. CD44 is a cell surface marker protein which is highly expressed in stem-like cells of several human cancers including brea...
Conference Paper
Full-text available
Introduction: Recent studies have shown that intra-tumor heterogeneity is the main cause of therapeutic resistance in cancer. Tumor tissue is composed of heterogeneous cellular populations with a hierarchical organization governed by stem/progenitor-like cells, also referred to as cancer stem-like cells (CSCs). Epithelial cell adhesion molecule (Ep...
Article
Full-text available
It has recently been reported that molecular targeting drugs fail to overcome the “oncogene/oncogenic signaladdiction” of cancer cells. Tumor tissue is composed of heterogeneous cancer cells, so that the therapeutic response is difficult to predict. Recent advance in cancer research has strongly suggests that cancer stem cells contribute to the for...
Article
Full-text available
Helicobacter pylori infection induces chronic inflammation that contributes to gastric tumorigenesis. Tumor necrosis factor (TNF-α) is a proinflammatory cytokine, and polymorphism in the TNF-α gene increases the risk of gastric cancer. We herein investigated the role of TNF-α in gastric tumorigenesis using Gan mouse model, which recapitulates human...
Conference Paper
Metastasis of tumor cells is a multi-step phenomenon including dissociation from primary site, intravasation, long-term circulation in the blood, extravasation, and colonization in the pre-metastatic niche in the distant organs. It is quite important that cancer cells are always exposed to redox stress throughout this muti-step metastatic phenomeno...
Article
Full-text available
Background Li-Fraumeni syndrome (LFS) is a hereditary cancer predisposition syndrome that is commonly associated with a germline mutation in the tumor suppressor gene p53. Loss of p53 results in increased expression of CD44, a cancer stem cell (CSC) marker, which is involved in the scavenging of reactive oxygen species (ROS). Here, we report a chan...
Article
Full-text available
In cancer metastasis, various environmental stressors attack the disseminating cells. The successful colonization of cancer cells in secondary sites therefore requires the ability of the cells to avoid the consequences of such exposure to the stressors. Here we show that orthotopic transplantation of a CD44 variant isoform-expressing (CD44v(+)) sub...
Conference Paper
EpCAM (Epithelial cell adhesion molecule: CD326) is a type I transmembrane glycoprotein that functions as an epithelial-specific cell-adhesion molecule. This molecule has long been recognized as one of the cancer stem cell markers, but the detailed function of EpCAM is still elusive. EpCAM is expressed in tumor cells in the vast majority of patient...
Article
Cancer stem cells (CSCs) , which are subset of tumor cells resistant to radiation and chemotherapy, are associated with malignant characteristics of tumor and possess both self-renewal ability and pluripotency for tumor formation. In the process of generating non-CSCs from CSCs, gene mutations and epigenetic changes are induced in those cells, resu...

Questions

Questions (111)
Question
Mounting evidence has shown that ABC (ATP-binding casette) transporter is responsible for the efflux of anti-cancer agents.
On the other hand, clinical trials to date using ABC transporter inhibitors have been disappointing ( Crit Rev Oncol Hematol. 2015 Nov;96(2):220-56. doi:10.1016/j.critrevonc.2015.05.012. ).
Ovarian cancer cells do not depend on ABC transporter to exhibit the therapeutic resistance?
Question
There are several transcriptional factors to induce complete EMT such as Snail, Slug, Twist, and ZEB1/2.
Partial EMT enables collective migration of cells as clusters of circulating tumor cells or emboli, further endorsing that cells in hybrid E(epithelial)/M(mesenchymal) hybrid phenotype might be the 'fittest' for metastasis.
Partial EMT brings about the aggressive metastatic cancer cells as compared with mesenchymal tumor cells.
That is why I would like to know what kind of transcriptional factor drives partial EMT.
Question
It has been reported that vitamin D drives the mesenchymal phenotype of QM-typed PDAC cells.
Epithelial to mesenchymal plasticity and differential response to therapies in pancreatic ductal adenocarcinoma
On the other hand, vitamin D changes pro-tumorigenic cancer-associated fibroblast (CAFs) into Merflin-positive anti-tumor fibroblasts.
Meflin-Positive Cancer-Associated Fibroblasts Inhibit Pancreatic Carcinogenesis
Taken together, how do you think whether vitamin D drives the malignant potential of PDAC?
Question
It has been reported that ABCB5, CD133, CD166, CD34, nestin, and c-kit stem cell antigens have been recognized as CSC marker of malignant melanoma.
However, given that malignant melanoma consists of stochastic model (also referred to as "mutation model"), it is difficult to identify the bona fide CSC marker of melanoma.
What is the most reliable marker of melanoma stem cells?
Question
I would like to know which type of distant metastasis corresponds to Paget "seed and soil" theory?
1. normal stem cell niches
2. perivascular niches
3. distant tissue niches
In mouse models, breast, lung, and gastrointestinal tumors establish premetastatic niches by secreting systemic factors such as VEGF-A, TGF-β, G-CSF, tumor necrosis factor (TNF) and lysyl oxidase (LOX) that induce expression of chemotactic proteins (S100A8, S100A9 and serum amyloid A3 (SAA3)), ECM-remodeling enzymes and exosomes into the circulation and directs various cells to induce pro-metastatic changes in the lung parenchyma microenvironment before DTCs arrive
Question
It is widely accepted that transcriptional factors (TF) including Snail, Slug, Twist, and ZEB1/2 contribute to epithelial-to-mesenchymal transition (EMT).
On the other hand, is there TF to promote mesenchymal-to-epithelial transition (MET)?
Question
It has been reported that Tumor-entrained neutrophils (TENs) inhibit metastatic seeding in the lungs by generating H2O2 and tumor secreted CCL2 is a critical mediator of optimal anti-metastatic entrainment of G-CSF-stimulated neutrophils.
On the other hand, neutrophil-derived leukotrienes aid the colonization of distant tissue by selectively expanding the sub-pool of cancer cells that retain high tumorigenic potential.
Question
Circulating tumor cells (CTCs) can also colonize their tumors of origin, in a process that we call “tumor self-seeding”. Self-seeding of breast cancer, colon cancer, and melanoma tumors in mice is preferentially mediated by aggressive CTCs, including those with bone, lung or brain metastatic tropism. The tumor-derived cytokines IL-6 and IL-8 acted as CTC attractants and the poor-prognosis markers MMP1/collagenase-1 and the actin cytoskeleton component fascin-1 as mediators of CTC infiltration into mammary tumors. Self-seeding can accelerate tumor growth, angiogenesis, and stromal recruitment through seed-derived factors including, in a breast.
Is there any possibility that not only CTCs but also cancer cells derived from distant organ metastatic disease show the self-seeding?
Question
CD44 variant 8-10 (CD44v9), which is generated by epithelial splicing regulatory protein 1 (ESRP1), contributes to the resistance to oxidative stress by the stabilization of xCT cystine transporter.
That is why CD44v9 mediated by xCT determines the malignant phenotype of gastric, breast, colorectal, tongue cancer cells.
Paradoxically,
Question
Triple negative breast cancer (TNBC) accounts for 10–20% of all cases of breast carcinoma and is characterized by the low expression of progesterone receptor (PR), estrogen receptor (ER), and human epidermal growth factor receptor 2 (HER2).
Pulmonary tumor embolism occurs when solid tumors seed the systemic circulation with individual cells, clusters of cells, or large tumor fragments. Emboli travel to the pulmonary vasculature, causing microvasculature obstruction. Furthermore, tumor emboli may activate the coagulation system, resulting in concomitant thrombotic obstruction.
Question
It was indicated that LC3 was expressed at a lower level in ovarian cancer tissues as compared to benign and borderline ovarian tumors. Furthermore, the expression of LC3 was lower in FIGO stages III and IV than in stages I and II. A diversity of studies implied that promoting autophagy-related cell death was required for up-regulation of LC3-II levels in ovarian cancer tissues and cells. ( )
This means that the low expression of LC-3 makes ovarian cancer cells refractory to autophagic cell death?

Network

Cited By
    • Institute of Urology,Tongji Hospital , Tongji Medical College,Huazhong University of Science and Technology, Wuhan 430030, China
    • Istituto Regina Elena - Istituti Fisioterapici Ospitalieri
    • University of Naples Federico II
    • Monash University (Australia)
    • Cancer Research Institute, Kanazawa University

Projects

Projects (3)
Project
To elucidate the metabolic reprogramming in cancer stem cells. Ref. Patrick S. Ward and Craig B. Thompson. Metabolic Reprogramming: A Cancer Hallmark Even Warburg Did Not Anticipate. Cancer Cell. 2012 Mar 20; 21(3): 297–308. Go J. Yoshida. Metabolic reprogramming: the emerging concept and associated therapeutic strategies. Journal of Experimental & Clinical Cancer Research 2015; 34: 111.
Project
To identify the molecular mechinery of autophagic cell death in RAS-driven cancer cells