Insights from the degradation mechanism of cyclin D into targeted therapy of the cancer cell cycle

Caudron-Herger, Maïwen; Diederichs, Sven

doi:10.1038/s41392-021-00732-y

Cited by 6 publications

(7 citation statements)

References 8 publications

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“…Moreover, we also found that the elevated expression of cyclin D1 (CCND1) induced by METTL3 overexpression could be reversed by YTHDF1 knockdown or FRAS1 knockdown. CCND1 which belongs to the highly conserved cyclin family, regulates cell cycle G1/S transition and promotes cell proliferation in multiple tumors [32][33][34]. Consistently, we also detected CDON, METTL3 and YTHDF1 protein expressions in five collected tumor samples as shown in Additional file 1: Fig.…”

Section: Fras1 Is a Target Of N6-methyladenosine Mettl3 In Nsclcsupporting

confidence: 78%

METTL3 promotes non-small cell lung cancer (NSCLC) cell proliferation and colony formation in a m6A-YTHDF1 dependent way

et al. 2022

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Background N6-methyladenosine (m6A) is the most common RNA modification, which plays a pivotal role in tumor development and progression. In this study, we assessed the role of m6A methyltransferase METTL3 in FRAS1-involved cell proliferation and colony formation of non-small cell lung cancer (NSCLC) cell lines. Methods Cell viability was analyzed by Cell Counting Kit (CCK-8) and colony formation. M6A RNA immunoprecipitation (IP), Ribosomal immunoprecipitation, RNA immunoprecipitation (RIP) were performed to verify the relationship between METTL3, FRAS1 and YTHDF1. Rescue experiments to confirm the regulatory mechanism of METTL3-FRAS1 promoted NSCLC cell proliferation through CDON by cooperating YTHDF1. Results We found that FRAS1 was correlated with poor prognosis in NSCLC patients, of which the transcript undergoes m6A modification regulated by METTL3. METTL3 silence reduced cell viability of NSCLC cells HCC827 and NCI-H1975, which could be restored by FRAS1 overexpression. The m6A modification of FRAS1 could be recognized by YTHDF1. FRAS1 silence or YTHDF1 silence could rescue the elevated NSCLC cell proliferation, colony formation, and tumor growth induced by METTL3 overexpression in vitro and in vivo. Conclusions Our study reveals that METTL3-FRAS1 plays a crucial role in NSCLC cell proliferation, colony formation, and tumor growth through the regulation of CDON by cooperating YTHDF1.

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Section: Fras1 Is a Target Of N6-methyladenosine Mettl3 In Nsclcsupporting

confidence: 78%

METTL3 promotes non-small cell lung cancer (NSCLC) cell proliferation and colony formation in a m6A-YTHDF1 dependent way

et al. 2022

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“…NSCLC, head and neck, renal cell, breast, pancreatic and colorectal cancers), partly by gene amplification, and is therefore an attractive therapeutic target. 33 , 34 Recently, multiple CDK4/6 inhibitors have been approved for the treatment of breast cancer. 33 In addition, several ongoing clinical trials are assessing the efficacy of palbociclib, abemaciclib and ribociclib in other cancers (e.g.…”

Section: Discussionmentioning

confidence: 99%

Clinical sequencing identifies potential actionable alterations in a high rate of urachal and primary bladder adenocarcinomas

et al. 2023

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“…The cyclin D-CDK4/6 complex is often hyperactivated in various tumours (e.g. NSCLC, head and neck, renal cell, breast, pancreatic and colorectal cancer) partly by gene ampli cation, and is therefore an attractive therapeutic target (33,34). Recently, multiple CDK4/6 inhibitors have been approved for the treatment of breast cancer (33).…”

Section: Discussionmentioning

confidence: 99%

“…NSCLC, head and neck, renal cell, breast, pancreatic and colorectal cancer) partly by gene ampli cation, and is therefore an attractive therapeutic target (33,34). Recently, multiple CDK4/6 inhibitors have been approved for the treatment of breast cancer (33). In addition, several clinical trials are ongoing to assess the e cacy of palbociclib, abemaciclib, or ribociclib in other cancers (e.g.…”

Section: Discussionmentioning

confidence: 99%

Clinical sequencing identifies potential actionable alterations in a high rate of urachal and primary bladder adenocarcinomas

Váradi

Nagy

Reis

et al. 2022

Preprint

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Administration of targeted therapies provides a promising treatment strategy for rare cancers such as urachal adenocarcinoma (UrC) or primary bladder adenocarcinoma (PBAC), however, the selection of appropriate drugs remains difficult. Therefore, in the present study, we aimed to establish a routine compatible methodological pipeline for the identification of the most important therapeutic targets and potentially effective drugs for UrC and PBAC. Next-generation sequencing using a 161 cancer driver gene panel was performed on 41 UrC and 13 PBAC samples. Clinically relevant alterations were filtered by four publicly available databases. Therapeutic interpretation has been performed by in silico evaluation of drug-gene interactions using an evidence-based decision support tool. After data processing, 45/54 samples (33 UrC and 12 PBAC) passed the quality control. The sequencing analyses revealed a total of 191 pathogenic SNVs in 68 genes. The most frequent gain-of-function mutations in UrC were found in KRAS (33%), MYC (15%), EGFR (9%) and ERBB2 (9%), while in PBAC KRAS (25%), MYC (25%), FLT3 (17%) and TERT (17%) were recurrently affected. The most frequently affected pathways in both tumour types were related to cell cycle regulation, DNA damage control and the MAPK/RAS pathway. Actionable mutations with at least one available, regulatory agency-approved drug could be identified for 31/33 (94%) of UrC and 8/12 (67%) of PBAC patients. In this study, we used a commercially available assay and developed a data processing pipeline for the detection and therapeutic interpretation of genetic alterations in two rare cancers. Our analyses revealed actionable mutations in a high rate of cases, including EGFR, BRCA, CCND1/2/3, ERBB2, METex14 suggesting a potentially feasible strategy for both UrC and PBAC treatment.

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Insights from the degradation mechanism of cyclin D into targeted therapy of the cancer cell cycle

Cited by 6 publications

References 8 publications

METTL3 promotes non-small cell lung cancer (NSCLC) cell proliferation and colony formation in a m6A-YTHDF1 dependent way

METTL3 promotes non-small cell lung cancer (NSCLC) cell proliferation and colony formation in a m6A-YTHDF1 dependent way

Clinical sequencing identifies potential actionable alterations in a high rate of urachal and primary bladder adenocarcinomas

Clinical sequencing identifies potential actionable alterations in a high rate of urachal and primary bladder adenocarcinomas

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