Characterizing the <i>KRAS</i> G12C mutation in metastatic colorectal cancer: a population-based cohort and assessment of expression differences in The Cancer Genome Atlas

Li, Meredith; Keshavarz-Rahaghi, Faeze; Ladua, Gale; Swanson, Lucas; Speers, C.; Renouf, Daniel J.; Lim, Howard John; Gill, Sharlene; Stuart, Heather; Yip, Stephen; Loree, Jonathan M.

doi:10.1177/17588359221097940

Cited by 2 publications

(1 citation statement)

References 28 publications

(45 reference statements)

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“…Future analysis of the effect of reducing reagents, including DTT, on the association of EDEM2 and TXNDC11 and the stability of unbound EDEM2 is needed. Recently, high expression of EDEM2 in several cancer cell lines, including glioma, 27,28,29) has been reported, although it is unclear whether high EDEM2 expression is related to cancer cell proliferation and poor prognosis via ERAD enhancement. Further investigations of this finding will contribute not only to the regulation of the basic molecular mechanisms of ERAD but also to tumor control.…”

Section: Resultsmentioning

confidence: 99%

Regulation of the ER-Resident Mannosidase EDEM2 in HEK293 Cells

Murase,

Kato,

Oh-hashi

2023

BPB Reports

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EDEM2 plays an important role as the first enzyme that acts during mannose trimming of N-glycosylated proteins in the ERAD machinery. Although EDEM2 expression has been reported to be transcriptionally regulated by the IRE1-sXBP1 pathway, very little is known about how endogenous EDEM2 protein expression is regulated. In this work, three different ER stress inducers were used to treat HEK293 cells. Thapsigargan slightly increased both EDEM2 mRNA and protein levels in the cells. Treatment with MG132 did not increase the level of mature EDEM2 protein, and a truncated form of the protein appeared. In SEL1L-deficient cells, there was a slight increase in EDEM2 protein as well as in TXNDC11, a protein that has been reported to form disulfide bonds with EDEM2. On the other hand, EDEM2 protein level decreased in TXNDC11-deficient cells. DTT treatment decreased EDEM2 and TXNDC11 protein levels in a time-dependent manner. The decrease in EDEM2 protein after DTT treatment was attenuated by treatment of the cells with MG132 and by SEL1L deficiency. These findings demonstrate that endogenous EDEM2 protein is regulated posttranscriptionally and that it is in part an SEL1L-mediated ERAD substrate.

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Section: Resultsmentioning

confidence: 99%

Regulation of the ER-Resident Mannosidase EDEM2 in HEK293 Cells

Murase,

Kato,

Oh-hashi

2023

BPB Reports

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Practical Implications of KRAS Mutation Status and Sidedness of Primary Tumour in Patients with Colorectal Cancer and Synchronous Liver Metastases: A Subset Analysis of the CoSMIC Study

Chan

Siriwardena

2022

Cancers

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Patients with colorectal cancer presenting with synchronous liver metastases have less favourable outcomes than those with primary-only disease. There is evidence of different genetic mutational signatures according to the sidedness of the primary tumour. KRAS mutations are key driver mutations in colorectal cancer progression. This post hoc analysis of the previously reported CoSMIC inception cohort explores the association between primary tumour sidedness and KRAS mutational status on the outcome of patients with colorectal cancer and synchronous liver metastases. Patients diagnosed with synchronous disease were recruited between April 2014 and March 2017 and, after exclusions, 83 patients undergoing colorectal primary KRAS mutation testing constituted the final study population. Data were collected prospectively on demographic profiles, treatment, and outcomes. Twenty-one patients (25%) had right-sided tumours and 62 (75%) had left-sided tumours, with 46 (55%) and 37 (45%) exhibiting wildtype and mutated KRAS, respectively. There was no difference in distribution of liver metastases by KRAS status (unilobar vs. bi-lobar; p = 0.58; Fisher’s Exact test) and no difference in 5-year survival according to KRAS mutation status (Log-rank test, p = 0.82) or tumour sidedness (p = 0.16). In summary, in this cohort of patients with colorectal cancer and synchronous liver metastases, neither KRAS mutation status nor tumour sidedness influenced survival.

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Characterizing the KRAS G12C mutation in metastatic colorectal cancer: a population-based cohort and assessment of expression differences in The Cancer Genome Atlas

Cited by 2 publications

References 28 publications

Regulation of the ER-Resident Mannosidase EDEM2 in HEK293 Cells

Regulation of the ER-Resident Mannosidase EDEM2 in HEK293 Cells

Practical Implications of KRAS Mutation Status and Sidedness of Primary Tumour in Patients with Colorectal Cancer and Synchronous Liver Metastases: A Subset Analysis of the CoSMIC Study

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