Exosomal miRNA-106b from cancer-associated fibroblast promotes gemcitabine resistance in pancreatic cancer

Fang, Yuan; Zhou, Wentao; Rong, Yefei; Kuang, Tiantao; Xu, Xuefeng; Wu, Wen-Chuan; Wang, Dansong; Lou, Wenhui

doi:10.1016/j.yexcr.2019.111543

Cited by 171 publications

(108 citation statements)

References 22 publications

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“…CAFs demonstrate a high degree of resistance to chemotherapeutics and can transfer this resistance to neighboring cancer cells via EV miRNAs. For instance, exosomes derived from gemcitabine-resistant CAFs contain high levels of miR-106a that, when taken up by recipient pancreatic cancer cells, promotes chemoresistance through the inhibition of the tumor suppressor TP53INP1 [160]. In ovarian cancer, CAF-derived exosomes express high levels of miR-98-5p that is transmitted to cells of the TME, leading to the development of cisplatin resistance by cancer cells through direct inhibition of cyclin-dependent kinase inhibitor 1A (CDKN1A, p21) [148].…”

Section: Caf-derived Evs Contents In Therapy Resistancementioning

confidence: 99%

The Role of Cancer-Associated Fibroblasts and Extracellular Vesicles in Tumorigenesis

Shoucair

Mello

Jabalee

et al. 2020

IJMS

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Extracellular vesicles (EVs) play a key role in the communication between cancer cells and stromal components of the tumor microenvironment (TME). In this context, cancer cell-derived EVs can regulate the activation of a CAF phenotype in TME cells, which can be mediated by several EV cargos (e.g., miRNA, proteins, mRNA and lncRNAs). On the other hand, CAF-derived EVs can mediate several processes during tumorigenesis, including tumor growth, invasion, metastasis, and therapy resistance. This review aimed to discuss the molecular aspects of EV-based cross-talk between CAFs and cancer cells during tumorigenesis, in addition to assessing the roles of EV cargo in therapy resistance and pre-metastatic niche formation.

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Section: Caf-derived Evs Contents In Therapy Resistancementioning

confidence: 99%

The Role of Cancer-Associated Fibroblasts and Extracellular Vesicles in Tumorigenesis

Shoucair

Mello

Jabalee

et al. 2020

IJMS

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“…In addition, TP53INP1 is also a stress protein, which has been indicated to play a tumor suppressive role by regulating metabolic homeostasis (137). Fang et al showed that CAF derives exosomal miR-106b, which promotes gemcitabine resistance by directly targeting TP53INP1 (138).…”

Section: Metabolic Reprogramming and Tme Acidosismentioning

confidence: 99%

The Role of Exosomal microRNA in Cancer Drug Resistance

et al. 2020

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Exosomes affect the initiation and progression of cancers. In the tumor microenvironment, not only cancer cells, but also fibroblasts and immunocytes secrete exosomes. Exosomes act as a communicator between cells by transferring different cargos and microRNAs (miRNAs). Drug resistance is one of the critical factors affecting therapeutic effect in the course of cancer treatment. The currently known mechanisms of drug resistance include drug efflux, alterations in drug metabolism, DNA damage repair, alterations of energy programming, cancer stem cells and epigenetic changes. Many studies have shown that miRNA carried by exosomes is closely associated with the development of drug resistance mediated by the above-mentioned mechanisms. This review article will discuss how exosomal miRNAs regulate the drug resistance.

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“…Communication between CAFs and tumor cells promotes the formation of a therapy-resistant phenotype in the latter [221]. For example, CAFs have been associated with the development of resistance to gemcitabine in pancreatic cancer through secretion of miRNA-106b [222]; to gefitinib in non-small cell lung cancer via secretion of IGF-1 and HGF [223]; to 5-fluorouracil in colorectal cancer [224]; to cisplatin in esophageal squamous cell cancer through secretion of PAI-1 [225] and TGFβ1 [226], in gastric cancer through secretion of miR-522 [227], IL-11, IL-6, and other cytokines and growth factors [228], and in lung adenocarcinoma due to secretion of IL-11 [229].…”

Section: Communication Between Cancer Cells and Surrounding Stromal Cmentioning

confidence: 99%

“…In response to therapy treatment, CAFs secrete microRNAs encapsulated into extracellular vesicles. After entering recipient tumor cells, miRNA-106b or miR-522 reduce cancer cells' sensitivity to the chemotherapy by targeting antiproliferative and pro-apoptotic protein TP53INP1 [222] and arachidonate lipoxygenase (ALOX15), leading to a decrease in the accumulation of lipid peroxides in cells and inhibition of ferroptosis [227]. The mechanism of action of miR-21 is based on targeting APAF1, which leads to impairment in the activation of caspase-3 and apoptosis [230].…”

Section: Communication Between Cancer Cells and Surrounding Stromal Cmentioning

confidence: 99%

“…Also, TGFβ1 [226], IL-6 [234,235], and GDNF [236] participate in CAF-mediated chemoresistance. Special attention should be paid to the fact that some of the above-mentioned molecules, namely miR-106b [222], miR-522 [227], IL-11 [229], PAI-1 [225], and GDNF [236] are secreted by CAFs in response to therapy.…”

Section: Communication Between Cancer Cells and Surrounding Stromal Cmentioning

confidence: 99%

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New Insights into Therapy-Induced Progression of Cancer

Shnaider

Ivanova

Malyants

et al. 2020

IJMS

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The malignant tumor is a complex heterogeneous set of cells functioning in a no less heterogeneous microenvironment. Like any dynamic system, cancerous tumors evolve and undergo changes in response to external influences, including therapy. Initially, most tumors are susceptible to treatment. However, remaining cancer cells may rapidly reestablish the tumor after a temporary remission. These new populations of malignant cells usually have increased resistance not only to the first-line agent, but also to the second- and third-line drugs, leading to a significant decrease in patient survival. Multiple studies describe the mechanism of acquired therapy resistance. In past decades, it became clear that, in addition to the simple selection of pre-existing resistant clones, therapy induces a highly complicated and tightly regulated molecular response that allows tumors to adapt to current and even subsequent therapeutic interventions. This review summarizes mechanisms of acquired resistance, such as secondary genetic alterations, impaired function of drug transporters, and autophagy. Moreover, we describe less obvious molecular aspects of therapy resistance in cancers, including epithelial-to-mesenchymal transition, cell cycle alterations, and the role of intercellular communication. Understanding these molecular mechanisms will be beneficial in finding novel therapeutic approaches for cancer therapy.

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Exosomal miRNA-106b from cancer-associated fibroblast promotes gemcitabine resistance in pancreatic cancer

Cited by 171 publications

References 22 publications

The Role of Cancer-Associated Fibroblasts and Extracellular Vesicles in Tumorigenesis

The Role of Cancer-Associated Fibroblasts and Extracellular Vesicles in Tumorigenesis

The Role of Exosomal microRNA in Cancer Drug Resistance

New Insights into Therapy-Induced Progression of Cancer

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