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| 1 | Heat shock protein 47 promotes tumor survival and therapy resistance by modulating AKT signaling via PHLPP1 in colorectal cancer显示文摘Objective:Heat shock protein 47(HSP47)is a collagen-specific molecular chaperone that facilitates collagen maturation.Its role in cancer remains largely unknown.In this study,we investigated the roles o f HSP47 in colorectal cancer(CRC)and therapy resistance.Methods:Expression o f HSP47 in CRC tissues was examined(1)in paired human CRC/adjacent normal tissues,using real time quantitative reverse transcription polymerase chain reaction(qRT-PCR),The Cancer Genome Atlas(TCGA)database,and 22 independent m icroarray databases(curated CRC).In vitro studies on several CRC cell lines(H C T 116,RKO and C C L228)with modulated HSP47 expression were conducted to assess cell viability and apoptosis(TU N EL assay and caspase-3/-7)during exposure to chemotherapy.AKT signaling and co-imm unoprecipitation studies were performed to examine HSP47 and PHLPP1 interaction.In vivo studies using tumor xenografts were conducted to assess the effects of HSP47 modulation on tum or growth and therapy response.Results:HSP47 was upregulated in CRC and was associated with poor prognosis in individuals with CRC.In vitro,HSP47 overexpression supported the survival of CRC cells,whereas its knockdown sensitized cells to 5-fluorouracil(5-FU).HSP47 promoted survival by inhibiting apoptosis,enhancing AKT phosphorylation,and decreasing expression of the AKT-specific phosphatase PHLPP1 when cells were exposed to chemotherapy.These effects were partly results of the interaction between HSP47 and PHLPP1,which decreased PHLPP1 stability and led to more persistent AKT activity.In vivoy HSP47 supported tumor growth despite 5-FU treatment.Conclusions:HSP47 supports the growth of CRC tumors and suppresses the efficacy of chemotherapy via modulation of AKT signaling. | Yijye Chern Peter Zhang Hyelim Ju Isabella T.Tai | 2020 | Cancer Biology & Medicine2020，17，2： | 3 |
| 2 | Bilateral trade of cultural goods显示文摘 | Anne-Ce'lia Disdier Silvio H T.Tai Lionel Fontagne' Thierry Mayer | | 0，，145： | 1 |
| 3 | Adaptive response of resistant cancer cells to chemotherapy显示文摘Despite advances in cancer therapeutics and the integration of personalized medicine,the development of chemoresistance in many patients remains a significant contributing factor to cancer mortality.Upon treatment with chemotherapeutics,the disruption of homeostasis in cancer cells triggers the adaptive response which has emerged as a key resistance mechanism.In this review,we summarize the mechanistic studies investigating the three major components of the adaptive response,autophagy,endoplasmic reticulum(ER)stress signaling,and senescence,in response to cancer chemotherapy.We will discuss the development of potential cancer therapeutic strategies in the context of these adaptive resistance mechanisms,with the goal of stimulating research that may facilitate the development of effective cancer therapy. | Yi-Jye Chern Isabella T.Tai | 2020 | Cancer Biology & Medicine2020，17，4： | 0 |
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