Elimination of head and neck cancer initiating cells through targeting glucose regulated protein78 signaling

Wu, Meng-Ju; Jan, Chia Ing; Tsay, Yeou Guang; Yu, Yau Hua; Huang, Chih Yang; Lin, Shu Chun; Liu, Chung Ji; Chen, Yu Syuan; Lo, Jeng‐Fan; Yu, Cheng Chia

doi:10.1186/1476-4598-9-283

Cited by 101 publications

(123 citation statements)

References 61 publications

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“…In addition, the association of low ROS level and radioresistance in breast CSCs has been reported (16). Previously, we have successfully enriched a subpopulation of HN-CICs derived from both SAS and OECM1 HNSCCs (7,9). Herein, we first aim to understand whether the intracellular level of ROS is relatively lower in HN-CICs.…”

Section: Resultsmentioning

confidence: 99%

Distinct Subpopulations of Head and Neck Cancer Cells with Different Levels of Intracellular Reactive Oxygen Species Exhibit Diverse Stemness, Proliferation, and Chemosensitivity

Chang¹,

Chen²,

Chou

et al. 2014

Cancer Research

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103

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Section: Resultsmentioning

confidence: 99%

Distinct Subpopulations of Head and Neck Cancer Cells with Different Levels of Intracellular Reactive Oxygen Species Exhibit Diverse Stemness, Proliferation, and Chemosensitivity

Chang¹,

Chen²,

Chou

et al. 2014

Cancer Research

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103

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“…2D and E). Recent reports suggest that OSCC possess the potential of cancer stem cell (CSC) or the tumor initiating cell-like properties, and presents characteristics of aggressive tumor (22,26). Based on these studies as well as our finding that let-7d level is low in metastatic OSCC patients, we further explored the relationship between let-7d and cancer stemness properties of OSCC.…”

Section: Silencing Let-7d Enhances Mesenchymal Stem-like and Chemo-mentioning

confidence: 99%

“…After the bottom layer solidified, 2 ml of a top agar-medium mixture [DMEM, 10% (v/v) FCS, 0.3% (w/v) agar] containing 2x10 4 cells was added and incubated at 37˚C for 4 weeks. The plates were stained with 0.5 ml 0.005% crystal violet, and the number of colonies was counted using a dissecting microscope (26).…”

Section: In Vitro Cell Invasion Analysis and Soft Agar Assay The 24-mentioning

confidence: 99%

Let-7d functions as novel regulator of epithelial-mesenchymal transition and chemoresistant property in oral cancer

et al. 2011

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Abstract. Oral squamous cell carcinoma (OSCC) is a prevalent cancer worldwide. Let-7 family has been shown to function as a tumor suppressor through regulating multiple oncogenic signaling. Recent study reported that combined underexpression of miR-205 and let-7d showed negative correlation with the survival prognosis of head and neck cancer patients. However, the let-7d-involved mechanism in regulating OSCC is still unclear. In this study, we first demonstrated that let-7d expression was significantly decreased while Twist and Snail expression was increased in OSCC cancer cell lines and primary cultures as compared to normal human oral keratinocyte cells. To further investigate the role of let-7d in OSCC, we applied the SPONGE method to knock down let-7d in OECM-1 and two primary OSCC cell types. The results showed that knockdown of let-7d promote epithelialmesenchymal transition (EMT) traits and migratory/invasive capabilities in OSCC cells. Furthermore, down-expression of let-7d significantly activated Twist and Snail expressions and chemo-resistant abilities of OSCC cells. Notably, overexpression of let-7d effectively reversed the EMT phenotype, blocked migratory/invasive abilities, and further increased the chemosensitivity in oral cancer tumor initiating ALDH1 + cells. In sum, these results show that let-7d negatively modulates EMT expression and also plays a role in regulating chemo-resistant ability in oral cancer. IntroductionHead and neck squamous cell carcinoma, including oral squamous cell carcinoma (OSCC), is the sixth most prevalent malignancy worldwide and accounts for approximately 8-10% of all cancers in Southeast Asia (1,2). The prognosis of OSCC remains dismal as more than 50% of the patients die of this disease or complications within 5 years under current therapies (2). To increase patient survival rate, investigations elucidating the mechanisms of tumorigenesis in OSCC are urgently needed (2). Some studies have suggested that subsets of cancer stem cells (CSC) or tumor initiating cells (TICs) are responsible for tumor progression as well as recurrence after conventional chemotherapy (3). However, there is lack of suitable markers for isolating the crucial subset of tumor cells that is capable of reforming new tumors in vivo and accounts for tumor relapse in OSCC, according to CSC hypothesis of tumorigenesis.MicroRNAs (miRNAs), highly conserved small RNA molecules that regulate gene expression, can act as cancer signatures, oncogenes or tumor suppressors (4). The ubiquitously expressed let-7/miR-98 family was one of the first mammalian miRNAs to be identified (5-8). Let-7 family members have been described as being down-regulated during cancer progression in various human cancers including lung, gastric, ovarian, colon cancer, leiomyoma and melanoma (5-13). Let-7d, a member of the let-7 family of miRNAs, has also been shown to act as tumor suppressor, most likely through targeting RAS (14) or high mobility group A2 (15). Let-7d regulates senescence of human cord blood-derived multipotent ste...

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“…An increased expression of GRP78 protein has been reported in various cancers, including astrocytoma (10) and breast (11), gastric (12), lung (13), and prostate cancers (14). Further studies have revealed that the overexpression of GRP78 contributes to apoptosis inhibition, cancer progression, metastasis and angiogenesis, and confers a resistance to antitumor therapies (15)(16)(17). In addition, numerous studies have indicated that the IRE1/X-box binding protein 1 (XBP1) and PERK/eIF2α/ATF4 pathways are important in the promotion of tumor survival and growth under stress conditions (18,19).…”

Section: Introductionmentioning

confidence: 99%

“…These pathophysiological conditions result in the disruption of the protein folding capacity and the buildup of unfolded and misfolded proteins within the ER, activating the UPR signaling pathway (5,6). Previous studies have demonstrated that the microenvironment of tumor cells resembles the physiologic ER stress, indicating that UPR plays an important role in cancer progression, malignancy and resistance to cancer therapy (15)(16)(17). Therefore, endogenous ER stress from the tumor microenvironment may contribute to the resistance of thyroid cancer cells to radiotherapy.…”

mentioning

confidence: 99%

Endoplasmic reticulum stress protects human thyroid carcinoma cell lines against ionizing radiation-induced apoptosis

Fan

Cui

et al. 2014

Molecular Medicine Reports

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Abstract. Radiotherapy is one of the most effective forms of cancer treatment, used in the treatment of a number of malignant tumors. However, the resistance of tumor cells to ionizing radiation remains a major therapeutic problem and the critical mechanisms determining radiation resistance are poorly defined. In the present study, a cellular endoplasmic reticulum (ER) stress microenvironment was established through the pretreatment of cultured thyroid cancer cells with tunicamycin (TM) and thapsigargin (TG), in order to mimic the ER stress response in a tumor microenvironment. This microenviroment was confirmed through the X-box binding protein 1 splice process, glucose-regulated protein 78 kD and ER degradation-enhancing α-mannosidase-like mRNA expression. A clonogenic assay was used to measure cancer cell resistance to 60 Co-γ following TM pretreatment; in addition, human C/EBP homologous protein (CHOP) mRNA expression was determined and apoptosis assays were performed. The results showed that TM or TG pretreatment inhibited CHOP expression and reduced the apoptotic rate of cells. Furthermore, the results demonstrated that the induced ER stress response rendered cancer cells more resistant to ionizing radiation-induced apoptosis. Therefore, the ER stress pathway may be a potential therapeutic target in order to improve the clinical efficiency of radiotherapy.

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Elimination of head and neck cancer initiating cells through targeting glucose regulated protein78 signaling

Cited by 101 publications

References 61 publications

Distinct Subpopulations of Head and Neck Cancer Cells with Different Levels of Intracellular Reactive Oxygen Species Exhibit Diverse Stemness, Proliferation, and Chemosensitivity

Distinct Subpopulations of Head and Neck Cancer Cells with Different Levels of Intracellular Reactive Oxygen Species Exhibit Diverse Stemness, Proliferation, and Chemosensitivity

Let-7d functions as novel regulator of epithelial-mesenchymal transition and chemoresistant property in oral cancer

Endoplasmic reticulum stress protects human thyroid carcinoma cell lines against ionizing radiation-induced apoptosis

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