TERT accelerates BRAF mutant–induced thyroid cancer dedifferentiation and progression by regulating ribosome biogenesis

Yu, Pengcheng; Qu, Ning; Zhu, Rui; Hu, Jiaqian; Han, Peizhen; Wu, Jiahao; Tan, Licheng; Gan, Hualei; He, Cong; Fang, Chuantao; Lei, Yubin; Li, Jian; He, Chenxi; Lan, Fei; Shi, Xiao; Wei, Wenjun; Wang, Yu; Ji, Qinghai; Yu, Fa-Xing; Wang, Yu-Long

doi:10.1126/sciadv.adg7125

Cited by 18 publications

(6 citation statements)

References 68 publications

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“…Another potential link of this risk factor with the invasiveness of the TC could be the length of telomeres and the telomerase activity. Thus, mutations of the gene TERT (i.e., telomerase reverse transcriptase) have been considered impactful on TC cell biology and dedifferentiation [ 32 , 33 ].…”

Section: Discussionmentioning

confidence: 99%

Papillary thyroid carcinoma: ≤ 10 mm does not always mean pN0. A multicentric real-world study

Amendola,

Piticchio,

Scappaticcio

et al. 2024

Updates Surg

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The incidence of papillary thyroid carcinoma (PTC) is increasing and PTC ≤ 10 mm (PTMC) accounts for most new diagnoses. PTMCs are not always low risk, as detection of lymph nodes metastasis (LNM) may occur. The purpose of the study was to analyze the clinical pattern, frequency, and independent risk factors of patients with PTMC and LNM. From January 2022 to June 2023, PTCs managed at CTO Hospital, Rome; Policlinico Vanvitelli, Naples; and Garibaldi Nesima Hospital, Catania were included. PTC management followed the same diagnostic–therapeutic procedures according to the ATA guidelines. Variables such as age, sex, maximum diameter, histologic evidence of LNM (HELNM +), Hashimoto’s thyroiditis (HT), multifocality, capsule invasion, and histological subtype were considered. PTCs were divided according to HELNM and size. Two hundred ninety-eight PTCs were included. PTMCs were 136 (45.6%) and LNM occurred in 27.2% of them. In the HELNM + group, analysis of PTMC vs ‘MacroPTC’ (PTC > 10 mm) did not show any statistical difference. Multivariate regression revealed that young age (OR 0.93; CI 95% 0.90–0.96; p < 0.01) and male sex (male OR 3.44; CI 95% 1.16–10.20; p = 0.03) were the only independent risk factors for HELNM + in PTMC. The risk of LNM in PTMC is not negligible; therefore, a careful evaluation by an expert thyroidologist is mandatory for patients with small thyroid nodule, especially in younger and male patients before excluding surgery. In the future, new tools are needed to detect early PTMC with LNM before surgery.

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Section: Discussionmentioning

confidence: 99%

Papillary thyroid carcinoma: ≤ 10 mm does not always mean pN0. A multicentric real-world study

Amendola,

Piticchio,

Scappaticcio

et al. 2024

Updates Surg

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“…9 The inhibition of rRNA production has been shown to inhibit tumor growth. 10 An inhibitor of RNA polymerase I exhibited antiproliferative activity in cancer cells and tumor xenografts, 11–13 further supporting the importance of ribosomal biogenesis for cancer cell population.…”

Section: Introductionmentioning

confidence: 91%

Pancreatic cancer cells exchange ribosomes through tunnelling nanotubes

Martínková,

Jansová,

Vorel

et al. 2024

Preprint

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SUMMARYPancreatic ductal adenocarcinoma (PDAC) is recognized as one of the most lethal types of cancer. Tunneling nanotubes (TNTs) are thin membranous intercellular communications, which allow cells to exchange intracellular material and promote cell fitness. We show here that PDAC cells increase the formation of TNTs upon exposure to gemcitabine and that these TNTs contain ribosomal components. In the PANC-1 cell line and in PDAC explants obtained from patient biopsies, we observe polyadenylated RNA and assembled 80S ribosomes within the TNTs, indicating the possibility of an intercellular transfer of translationally active ribosomes. Using cells with labelled small ribosomal subunits (40S), we demonstrate active transport of the ribosomal subunit via TNTs to recipient cells. Our results show that PDAC cells can exchange components of the translational machinery, including mRNA, which may contribute to the resistance to therapy, highlighting the potential of targeting TNT dynamics as a therapeutic approach for PDAC.HighlightsPDAC cells derived from tumor biopsy samples form tunneling nanotubes in 2D cultureFormation of tunneling nanotubes is stimulated by gemcitabine5.8S ribosomal RNA is transferred in PDAC via activated tunneling nanotubesPolyadenylated RNA is present in tunneling nanotubesRibosomal components are detected in activated tunneling nanotubesPDAC cells exchange assembled ribosomes via tunneling nanotubesRibosomes are transferred via TNTs to recipient cells, incorporated into ribosomes

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“…Several studies have reported an association between the V600E variant and aggressive disease features such as RAI refractoriness, lymph node metastases, locoregional invasion, and recurrence ( 64 , 67 , 69 ). Interestingly, PTCs with coexisting mutations in BRAF and the telomerase reverse transcriptase (TERT) promoter are associated with aggressive clinicopathological characteristics, more so than either mutation alone ( 70 , 71 ). On the other hand, RAS mutations occur mostly in follicular-variant PTC and non-invasive follicular thyroid neoplasm, which have a genomic profile more similar to FTC.…”

Section: Mutational Landscape Of Tcmentioning

confidence: 99%

Emerging therapeutic options for follicular-derived thyroid cancer in the era of immunotherapy

Turner,

Hamidi,

Ouni

et al. 2024

Front. Immunol.

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Although most follicular-derived thyroid cancers are well differentiated and have an overall excellent prognosis following treatment with surgery and radioiodine, management of advanced thyroid cancers, including iodine refractory disease and poorly differentiated/undifferentiated subtypes, is more challenging. Over the past decade, better understanding of the genetic drivers and immune milieu of advanced thyroid cancers has led to significant progress in the management of these patients. Numerous targeted kinase inhibitors are now approved by the U.S Food and Drug administration (FDA) for the treatment of advanced, radioiodine refractory differentiated thyroid cancers (DTC) as well as anaplastic thyroid cancer (ATC). Immunotherapy has also been thoroughly studied and has shown promise in selected cases. In this review, we summarize the progress in the understanding of the genetic landscape and the cellular and molecular basis of radioiodine refractory-DTC and ATC, as well as discuss the current treatment options and future therapeutic avenues.

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TERT accelerates BRAF mutant–induced thyroid cancer dedifferentiation and progression by regulating ribosome biogenesis

Cited by 18 publications

References 68 publications

Papillary thyroid carcinoma: ≤ 10 mm does not always mean pN0. A multicentric real-world study

Papillary thyroid carcinoma: ≤ 10 mm does not always mean pN0. A multicentric real-world study

Pancreatic cancer cells exchange ribosomes through tunnelling nanotubes

Emerging therapeutic options for follicular-derived thyroid cancer in the era of immunotherapy

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