Characterization of KLHL14 anti-oncogenic action in malignant mesothelioma

Canciello, Angelo; Domínguez, Reyes Benot; Barboni, Barbara; Giordano, Antonio; Morrione, Andrea

doi:10.1016/j.heliyon.2024.e27731

Cited by 2 publications

(3 citation statements)

References 40 publications

(64 reference statements)

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“…It has recently been shown that KLHL14 anti-oncogenic action in malignant mesothelioma is linked to changes in its nuclear-cytoplasmic shuttling in response to oncogenic stimuli [ 7 ]. For this reason, we asked how Klhl14 was distributed in thyroid cells and whether neoplastic transformation could alter its subcellular localization.…”

Section: Resultsmentioning

confidence: 99%

“…Another relevant aspect to consider is Klhl14 localization. Klhl14 has been originally detected in the ER and cytoplasm, consistently with its role of Cullin-RING Ligase 3 complex component [ 6 ], although recently it has been found expressed in the nucleus of malignant mesothelioma cells, and to shuttle between nucleus and cytoplasm in response to Tumor Growth Factor-β [ 7 ]. Accordingly, our data show that Klhl14 is localized in both the cytoplasm and nucleus of thyroid follicular cells, with a lower fraction in the nucleus of Ras-transformed cells compared to that of normal cells.…”

Section: Discussionmentioning

confidence: 99%

“…More recently, KLHL14 was reported to be involved in different human cancers. It has been shown that KLHL14 is frequently inactivated by somatic mutation in Diffuse Large B-Cell Lymphoma, causing the improper activation of NF-kB pathway through impaired quality control of B-cell receptor [ 6 ], and it is found to play an anti-oncogenic role in malignant mesothelioma, where its expression as well as its subcellular localization depend on TGF-β/EMT signaling [ 7 ]. Conversely, KLHL14 was found upregulated in ovarian cancer and in endometrial carcinoma, specifically in patients with poor prognosis [ 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

KLHL14 is a tumor suppressor downregulated in undifferentiated thyroid cancer

Esposito,

Migliaccio,

Credendino

et al. 2024

Cell Death Discov.

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KLHL14 is a substrate-binding subunit of Cullin-RING ligase 3 ubiquitin ligase complex, highly enriched in thyroid since early embryonic development, together with its antisense RNA KLHL14-AS. We have previously demonstrated that Klhl14-AS is a competing endogenous RNA regulating several differentiation and survival factors in thyroid cancer, acting as tumor suppressor. Recently, also KLHL14 has been shown to function as tumor suppressor in diffuse large B-cell lymphoma and in malignant mesothelioma. Here we show that KLHL14 expression is strongly reduced in anaplastic thyroid cancer, the less differentiated and most aggressive type of thyroid neoplasia. Such reduction is reproduced in different in vivo and in vitro models of thyroid cancer, being invariably associated with loss of differentiation. When Klhl14 expression is rescued in thyroid transformed cells, it reduces the cell proliferation rate and increase the number of apoptotic cells. On the other side, Klhl14 loss of function in normal thyroid cells affects the expression of several regulatory as well as functional thyroid markers. All these findings suggest that KLHL14 could be considered as a novel tumor suppressor in thyroid cancer, by also revealing its physiological role in the maintenance of a fully differentiated and functional thyroid phenotype.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

KLHL14 is a tumor suppressor downregulated in undifferentiated thyroid cancer

Esposito,

Migliaccio,

Credendino

et al. 2024

Cell Death Discov.

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KLHL14 and E-Cadherin Nuclear Co-Expression as Predicting Factor of Nonfunctioning PitNET Invasiveness: Preliminary Study

Berardinelli,

Russo,

Canciello

et al. 2024

JCM

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Background/Objectives. Novel diagnostic and therapeutic approaches are needed to improve the clinical management of nonfunctioning pituitary neuroendocrine tumors (NF-PitNETs). Here, the expression of two proteins controlling the epithelial–mesenchymal transition (EMT)—an underlying NF-PitNET pathogenic mechanism—were analyzed as prognostic markers: E-cadherin (E-Cad) and KLHL14. Methods. The immunohistochemistry characterization of KLHL14 and E-Cad subcellular expression in surgical specimens of 12 NF-PitNET patients, with low and high invasiveness grades (respectively, Ki67+ < and ≥3%) was carried out. Results. The analysis of healthy vs. NF-PitNET tissues demonstrated an increased protein expression and nuclear translocation of KLHL14. Moreover, both E-Cad and KLHL14 shifted from a cytoplasmic (C) form in a low invasive NF-PitNET to a nuclear (N) localization in a high invasive NF-PitNET. A significant correlation was found between E-Cad/KLHL14 co-localization in the cytoplasm (p = 0.01) and nucleus (p = 0.01) and with NF-PitNET invasiveness grade. Conclusions. Nuclear buildup of both E-Cad and KLHL14 detected in high invasive NF-PitNET patients highlights a novel intracellular mechanism governing the tumor propensity to local invasion (Ki67+ ≥ 3%). The prolonged progression-free survival trend documented in patients with lower KLHL14 expression further supported such a hypothesis even if a larger cohort of NF-PitNET patients have to be analyzed to definitively recognize a key prognostic role for KLHL14.

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Characterization of KLHL14 anti-oncogenic action in malignant mesothelioma

Cited by 2 publications

References 40 publications

KLHL14 is a tumor suppressor downregulated in undifferentiated thyroid cancer

KLHL14 is a tumor suppressor downregulated in undifferentiated thyroid cancer

KLHL14 and E-Cadherin Nuclear Co-Expression as Predicting Factor of Nonfunctioning PitNET Invasiveness: Preliminary Study

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