Kinesin-5 Contributes to Spindle-length Scaling in the Evolution of Cancer toward Metastasis

Yang, Ching-Feng; Tsai, Wan‐Yu; Chen, Wei-An; Liang, Kai Ming; Pan, Cheng-Ju; Lai, Pei-Lun; Yang, Pan‐Chyr; Huang, Hsiao-Chun

doi:10.1038/srep35767

Cited by 14 publications

(22 citation statements)

References 43 publications

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“…Inspired by such limitations, we used a repeated sphere-forming assay as a strategy to select a malignant cell line that was phenotypically stable. This is conceptually parallel to our previous establishment of a series of metastatic cell lines using repeated invasion assays 15,16 . Such model cell lines have been used to identify genes or cellular phenotypes that are associated with metastasis 16,17 .…”

Section: Introductionmentioning

confidence: 67%

“…This is conceptually parallel to our previous establishment of a series of metastatic cell lines using repeated invasion assays 15,16 . Such model cell lines have been used to identify genes or cellular phenotypes that are associated with metastasis 16,17 . In this study, with a repeated sphere-forming assay, we aimed to select a malignant clone from a HCT116 CRC cell line.…”

Section: Introductionmentioning

confidence: 67%

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Selection of a Malignant Subpopulation from a Colorectal Cancer Cell Line

Lai

Chen

Feng

et al. 2019

Preprint

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Colorectal cancer (CRC) is a leading cause of death from cancer worldwide. Thus, there is an emerging need for new experimental models that allow identification and validation of biomarkers for CRC-specific progression. In this study, we propose a repeated sphere-forming assay as a strategy to select a malignant subpopulation from a CRC line, HCT116. We validated our assay by confirming that three canonical stemness markers, Nanog, Oct4, and Lgr5, were up-regulated in the sphere state at every generation of the selection assay. The resulting line, after eight rounds of selection, exhibited an increased sphere-forming capacity in vitro and tumorgenicity in vivo. Furthermore, dipeptidase 1 (DPEP1) was identified as the major differentially expressed gene in the selected clone, and depletion of DPEP1 suppressed the elevated sphere-forming capacity in vitro and tumorgenicity in vivo. Overall, we have established an experimental strategy for the isolation of a malignant subpopulation from a CRC cell line. Results from our model also suggested that DPEP1 can serve as a promising prognostic biomarker for CRC.

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Section: Introductionmentioning

confidence: 67%

Section: Introductionmentioning

confidence: 67%

Selection of a Malignant Subpopulation from a Colorectal Cancer Cell Line

Lai

Chen

Feng

et al. 2019

Preprint

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“…These defects contribute to tumor heterogeneity and cancer progression [81]. Additional chromosomes pose a challenge for mitotic cells, as they require larger spindles to ensure that all chromosomes are associated with MTs prior to anaphase onset [82,83,84,85]. We propose that dynamic changes in bipolar spindle length, driven by cortical dynein activity, contributes to the spindle length requirements for chromosome capture and alignment, with particular relevance to cancer contexts where chromosome number is increased.…”

Section: Resultsmentioning

confidence: 98%

Modeling reveals cortical dynein-dependent fluctuations in bipolar spindle length

Mercadante

Manning

Olson

2020

Preprint

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Proper formation and maintenance of the mitotic spindle is required for faithful cell division. While much work has been done to understand the roles of the key force components of the mitotic spindle, identifying the implications of force perturbations in the spindle remains a challenge. We developed a computational framework of the minimal force requirements for mitotic progression and used experimental approaches to further define and validate the model. Through simulations, we show that rather than achieving and maintaining a constant bipolar spindle length, oscillations in pole to pole distance occur that coincide with microtubule binding and force generation by cortical dynein. In the context of high kinesin-14 (HSET) activity, we reveal the requirement of high cortical dynein activity for bipolar spindle formation.

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“…In order to overcome the aforementioned limitations, the present study used a repeated sphere-forming assay as a strategy to select a malignant subpopulation that was phenotypically stable. Conceptually, this strategy is similar to the previous establishment of a series of metastatic cell lines using repeated invasion assays (16,17). Such model cell lines have been used to identify genes or cellular phenotypes that are associated with metastasis (17,18).…”

Section: Selection Of a Malignant Subpopulation From A Colorectal Canmentioning

confidence: 99%

Selection of a malignant subpopulation from a colorectal cancer cell line

et al. 2020

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Colorectal cancer (CRC) is a leading cause of cancer-associated mortality worldwide; therefore, there is an emerging need for novel experimental models that allow for the identification and validation of biomarkers for CRC-specific progression. In the present study, a repeated sphere-forming assay was used as a strategy to select a malignant subpopulation from a CRC cell line, namely HCT116. The assay was validated by confirming that canonical stemness markers were upregulated in the sphere state at every generation of the selection assay. The resulting subpopulation, after eight rounds of selection, exhibited increased sphere-forming capacity in vitro and increased tumorigenicity in vivo. Furthermore, dipeptidase 1 (DPEP1) was identified as the major differentially expressed gene in the selected clone, and its depletion suppressed the elevated sphere-forming capacity in vitro and tumorigenicity in vivo. Overall, the present study established an experimental strategy to isolate a malignant subpopulation from a CRC cell line. Additionally, results from the present model revealed that DPEP1 may serve as a promising prognostic biomarker for CRC.

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Kinesin-5 Contributes to Spindle-length Scaling in the Evolution of Cancer toward Metastasis

Cited by 14 publications

References 43 publications

Selection of a Malignant Subpopulation from a Colorectal Cancer Cell Line

Selection of a Malignant Subpopulation from a Colorectal Cancer Cell Line

Modeling reveals cortical dynein-dependent fluctuations in bipolar spindle length

Selection of a malignant subpopulation from a colorectal cancer cell line

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