Role of asparagine synthetase in doxorubicin-induced resistance

Lin, Li‐Hsun; Lin, Szu‐Ting; Chou, Hsiu‐Chuan

doi:10.1016/j.bgm.2013.07.003

Cited by 5 publications

(5 citation statements)

References 6 publications

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“…Within the molecular pathways of DOX insensitivity or resistance, we identified for example high expression of Asns and Trib3 . Asns , encodes by asparagine synthetase, a protein known to induce DOX resistance in uterine cancer [ 30 ] and ALL [ 31 ] and has been proposed as a predictive biomarker for ovarian cancer and a therapeutic target for non‐Hodgkin's lymphoma. [ 32 ] Similarly, the pseudokinase TRIB3 expression is induced in response to cellular stress [ 33 ] and protects against the apoptotic effects of DOX in gastric cancer.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…These examples illustrate the potential of ALTEN to identify the molecular pharmacological mechanisms and multidrug resistance, one of the current grand challenges of cancer therapy. [30] Cancer immunotherapy, especially checkpoint blockade, revolutionized the landscape of cancer treatment and significantly increased patient survival in a range of cancers. [36] However, a major challenge to the study of the effects of drugs that target the immune system is that current conventional preclinical models-cocultures or PDXs-cannot to recapitulate the complex immune lineages and cellular niches of the tumor microenvironment, thus limiting the analysis of mechanistic effects of immunotherapy.…”

Section: Discussionmentioning

confidence: 99%

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ALTEN: A High‐Fidelity Primary Tissue‐Engineering Platform to Assess Cellular Responses Ex Vivo

et al. 2022

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To fully investigate cellular responses to stimuli and perturbations within tissues, it is essential to replicate the complex molecular interactions within the local microenvironment of cellular niches. Here, the authors introduce Alginate‐based tissue engineering (ALTEN), a biomimetic tissue platform that allows ex vivo analysis of explanted tissue biopsies. This method preserves the original characteristics of the source tissue's cellular milieu, allowing multiple and diverse cell types to be maintained over an extended period of time. As a result, ALTEN enables rapid and faithful characterization of perturbations across specific cell types within a tissue. Importantly, using single‐cell genomics, this approach provides integrated cellular responses at the resolution of individual cells. ALTEN is a powerful tool for the analysis of cellular responses upon exposure to cytotoxic agents and immunomodulators. Additionally, ALTEN's scalability using automated microfluidic devices for tissue encapsulation and subsequent transport, to enable centralized high‐throughput analysis of samples gathered by large‐scale multicenter studies, is shown.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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ALTEN: A High‐Fidelity Primary Tissue‐Engineering Platform to Assess Cellular Responses Ex Vivo

et al. 2022

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“…It has now become clear that the activation of ER stress is a common phenomenon in tumorigenesis (Schewe et al 2008;Hazari et al 2016;Bi et al 2005). The altered expression of ER stress proteins has been observed in various cancer types, including lung cancer (Tsai et al 2013), breast cancer (Kim et al 2016), colon cancer (Ryan et al 2016), gastric cancer (Shen et al 2015), pancreatic cancer (Niu et al 2015), liver cancer (Shuda et al 2003;Al-Rawashdeh et al 2010), prostate cancer (Storm et al 2016;Liu et al 2017), kidney cancer (Fu et al 2010), skin cancer (Shimizu et al 2017), uterine cancer (Lin et al 2013), ovarian cancer (Cubillos-Ruiz et al 2015), leukemia (Buontempo et al 2016), myeloma (Zhong et al 2016), and gliobastoma (Epple et al 2013).…”

Section: Evidence Of Upr Involvement In Cancermentioning

confidence: 99%

Role of the unfolded protein response in determining the fate of tumor cells and the promise of multi-targeted therapies

Shen

Johnson

Vesey

et al. 2018

Cell Stress and Chaperones

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Although there have been advances in our understanding of carcinogenesis and development of new treatments, cancer remains a common cause of death. Many regulatory pathways are incompletely understood in cancer development and progression, with a prime example being those related to the endoplasmic reticulum (ER). The pathological sequelae that arise from disruption of ER homeostasis are not well defined. The ER is an organelle that is responsible for secretory protein biosynthesis and the quality control of protein folding. The ER triggers an unfolded protein response (UPR) when misfolded proteins accumulate, and while the UPR acts to restore protein folding and ER homeostasis, this response can work as a switch to determine the death or survival of cells. The treatment of cancer with agents that target the UPR has shown promising outcomes. The UPR has wide crosstalk with other signaling pathways. Multi-targeted cancer therapies which target the intersections within signaling networks have shown synergistic tumoricidal effects. In the present review, the basic cellular and signaling pathways of the ER and UPR are introduced; then the crosstalk between the ER and other signaling pathways is summarized; and ultimately, the evidence that the UPR is a potential target for cancer therapy is discussed. Regulation of the UPR downstream signaling is a common therapeutic target for different tumor types. Tumoricidal effects achieved from modulating the UPR downstream signaling could be enhanced by phosphodiesterase 5 (PDE5) inhibitors. Largely untapped by Western medicine for cancer therapies are Chinese herbal medicines. This review explores and discusses the value of some Chinese herbal extracts as PDE5 inhibitors.

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“…It has now become clear that the activation of ER stress is a common phenomenon in tumourigenesis [80][81][82]. The altered expression of ER stress proteins has been observed in various cancer types, including lung [83], breast [84], colon [85], gastric [86], pancreatic [87], liver [88,89], prostate [90,91], kidney [37], skin [92], uterine [93], and ovarian cancers [94], leukaemia [95], myeloma [96] and glioblastoma [97].…”

Section: Er Stress Levels In Cancersmentioning

confidence: 99%

The role of the adipose tissue microenvironment in kidney cancer

Shen¹

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Obesity increases the risk of tumourigenesis, but paradoxically may predict better prognosis after cancer has been diagnosed. There is a general lack of understanding of interactions between cancer cells and adipose tissue. Obesity is characterised by activated endoplasmic reticulum (ER) stress and increased infiltration of macrophages in the adipose tissue. Little is known about the connection between the ER stress and infiltration of macrophages in the adipose tissue. Additionally, the impact of each characteristic on the biology of cancer cells is unclear. This PhD project attempted to define the adipose tissue microenvironment in the setting of cancer, in particular, kidney cancer. The thesis adds knowledge that helps to define the heterogeneous adipose tissue microenvironment and its functions in cancer development.The thesis is presented as a literature review (Chapter 1) followed by four original research sections (Chapters 2-5) that have, in some cases, been published (Chapter 2) or submitted (Chapters 3 and 4).The literature review (Chapter 1) will initially introduce the epidemiology, pathophysiology and prognostic factors for kidney cancer, followed by a summary of the advances in biomarker discovery in renal cell carcinoma (RCC). The literature review then introduces the structure, function and signaling pathways of the ER, followed by a discussion of the involvement of ER stress in cancer.The crosstalk between obesity, cancer and ER stress is also discussed. Finally, the role of macrophages in the tumour microenvironment is summarised.Chapter 2 is an immunohistochemistry-based retrospective cross-sectional study. Software-assisted quantification of staining intensity and proportion of positive pixels was applied to measure expression of glucose-regulated-protein-78/GRP78 (an ER stress marker) in archived specimens of renal tumour tissues (n=114), adjacent non-neoplastic renal tissues (n=68), and perinephric adipose tissues (n=60) in participants diagnosed with clear cell RCC (ccRCC), the commonest subtype of the RCC. Results demonstrated that GRP78 was not an optimal risk stratification marker for ccRCC.However, upregulated GRP78 in perinephric adipose tissue may be linked with a lower chance of metastasis.Chapter 3 introduces a liquid-overlay based method to generate reproducible and functional mature adipocyte spheroids using human perinephric adipose tissue-derived mesenchymal stem cells and the murine 3T3-L1 cell line. The established adipocyte spheroids were responsive to the ER stress activator, tunicamycin. and could secrete adiponectin, monocyte chemoattractant protein-1 (MCP-1) and interleukin/IL-8. Hence, the three-dimensional culture platform was able to serve as an adipose tissue microenvironment that could be applied in in vitro experiments.ii In Chapter 4, macrophage behaviour in the adipose tissue microenvironment was investigated using the 3D culture platform introduced in Chapter 3. Co-culture experiments were performed to measure the polarisation, migration and invasion of murine an...

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Role of asparagine synthetase in doxorubicin-induced resistance

Cited by 5 publications

References 6 publications

ALTEN: A High‐Fidelity Primary Tissue‐Engineering Platform to Assess Cellular Responses Ex Vivo

ALTEN: A High‐Fidelity Primary Tissue‐Engineering Platform to Assess Cellular Responses Ex Vivo

Role of the unfolded protein response in determining the fate of tumor cells and the promise of multi-targeted therapies

The role of the adipose tissue microenvironment in kidney cancer

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