SLC39A4 expression is associated with enhanced cell migration, cisplatin resistance, and poor survival in non-small cell lung cancer

Wu, Dongming; Teng, Liu; Deng, Shi‐Hua; Han, Rong; Xu, Ying

doi:10.1038/s41598-017-07830-4

Cited by 30 publications

(34 citation statements)

References 41 publications

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“…Lung cancer tissue arrays (HLugA180Su05) were purchased from Shanghai Outdo Biotech Co, Ltd (Shanghai, China). Immunohistochemistry (IHC) for PLEK2 protein expression was performed and scored as previously described . Scores of 0–2 were classified as low expression and scores >2 were classified as high expression.…”

Section: Methodsmentioning

confidence: 99%

PLEK2 mediates metastasis and vascular invasion via the ubiquitin‐dependent degradation of SHIP2 in non‐small cell lung cancer

Deng

Zhou³

et al. 2019

Intl Journal of Cancer

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Metastasis is the leading cause of death for non‐small cell lung cancer (NSCLC) patients. However, how lung cancer cells invade blood vessels during metastasis remains unclear. Here, based on bioinformatics analyses, we found that PLEK2 might regulate NSCLC migration and vascular invasion. As little is known about the function of PLEK2 in NSCLC, we aimed to clarify this. We demonstrated that PLEK2 was significantly upregulated in transforming growth factor beta 1 (TGF‐β1)‐treated NSCLC cells through ELK1 transcriptional activation, highly expressed in NSCLC tissues, and negatively correlated with NSCLC overall survival. Meanwhile, PLEK2 overexpression significantly promoted NSCLC epithelial‐to‐mesenchymal transition (EMT) and migration, human lung microvascular endothelial cells endothelial‐to‐mesenchymal transition (EndoMT), and the destruction of vascular endothelial barriers. Moreover, PLEK2 knockdown inhibited TGF‐β1‐induced EMT and EndoMT. Furthermore, PLEK2 was found to directly interact with SHIP2 and target it for ubiquitination and degradation in NSCLC cells. Next, we confirmed that SHIP2 overexpression inhibits NSCLC EMT, migration and invasion and showed that PLEK2 overexpression can activate SHIP2‐associated TGF‐β/PI3K/AKT signaling. Our results suggest that PLEK2 could be a novel prognostic marker and potential therapeutic target for NSCLC metastasis and vascular invasion.

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Section: Methodsmentioning

confidence: 99%

PLEK2 mediates metastasis and vascular invasion via the ubiquitin‐dependent degradation of SHIP2 in non‐small cell lung cancer

Deng

Zhou³

et al. 2019

Intl Journal of Cancer

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“…Accordingly, chelating zinc has been explored as a means to stop proliferative growth of cancer tissues [22]. The additional zinc seen in cancers is usually supplied by various zinc transporters from the SLC39A family [23] [24][25][26]. Two close homologues within this family, ZIP6 (SLC39A6, also known as LIV-1) and ZIP10 (SLC39A10) [27,28], with a 43.5% sequence identity, are on the same clade of the ZIP family phylogenetic tree [29] and have both been independently implicated in cancer [23,29].…”

Section: Cellular and Molecular Life Sciencesmentioning

confidence: 99%

The ZIP6/ZIP10 heteromer is essential for the zinc-mediated trigger of mitosis

Nimmanon

Ziliotto

Ogle

et al. 2020

Cell. Mol. Life Sci.

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Zinc has been known to be essential for cell division for over 40 years but the molecular pathways involved remain elusive. Cellular zinc import across biological membranes necessitates the help of zinc transporters such as the SLC39A family of ZIP transporters. We have discovered a molecular process that explains why zinc is required for cell division, involving two highly regulated zinc transporters, as a heteromer of ZIP6 and ZIP10, providing the means of cellular zinc entry at a specific time of the cell cycle that initiates a pathway resulting in the onset of mitosis. Crucially, when the zinc influx across this heteromer is blocked by ZIP6 or ZIP10 specific antibodies, there is no evidence of mitosis, confirming the requirement for zinc influx as a trigger of mitosis. The zinc that influxes into cells to trigger mitosis additionally changes the phosphorylation state of STAT3 converting it from a transcription factor to a protein that complexes with this heteromer and pS 38 Stathmin, the form allowing microtubule rearrangement as required in mitosis. This discovery now explains the specific cellular role of ZIP6 and ZIP10 and how they have special importance in the mitosis process compared to other ZIP transporter family members. This finding offers new therapeutic opportunities for inhibition of cell division in the many proliferative diseases that exist, such as cancer.

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“…The majority of patients with NSCLC are diagnosed with advanced tumors, and the 5-year survival rates in NSCLC range from 73% in stage IA disease to 13% in stage IV disease, worldwide (4). Despite great progress in therapeutic approaches for cancer treatment, such as surgery, chemotherapy, radiotherapy and targeted therapy, the prognosis and outcomes remain poor (5). To improve the management of NSCLC, efforts should be made in the development of novel and efficient strategies for diagnosis, prognosis and treatment.…”

Section: Introductionmentioning

confidence: 99%

Upregulated miR‑665 expression independently predicts poor prognosis of lung cancer and facilitates tumor cell proliferation, migration and invasion

Xia

Zhu

et al. 2020

Oncol Lett

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Non-small cell lung cancer (NSCLC) is one of the leading causes of global cancer-associated mortality. Aberrant microRNAs (miRs) have been reported to be involved in the pathogenesis of various cancer types. The present study aimed to investigate the expression profile and prognostic value of miR-665 in patients with NSCLC, and to analyze its functional role in tumor progression using NSCLC cells. Reverse transcription-quantitative PCR was used to estimate the expression levels of miR-665. Kaplan-Meier survival curves and Cox regression analysis were performed to evaluate the prognostic value of miR-665. The effects of miR-665 on NSCLC cell proliferation, migration and invasion were examined by cell transfection, and the target gene of miR-665 was explored. miR-665 expression was elevated in the tissue and cell samples of NSCLC. This increased miR-665 expression was associated with lymph node metastasis and TNM stage. An independent association between miR-665 and overall survival was identified in patients with NSCLC. When regulating the expression levels of miR-665 in vitro, NSCLC cell proliferation, migration and invasion were enhanced by overexpression of miR-665, but were inhibited by knockdown of miR-665. The luciferase activity results indicated that the protein tyrosine phosphatase receptor type B (PTPRB) was a direct target of miR-665 in NSCLC cells. The present study provided evidence for the clinical significance of a decreased expression of miR-665 in the prognosis of NSCLC. Upregulation of miR-665 contributed to tumor cell proliferation, migration and invasion by targeting PTPRB, suggesting the potential of miR-665 as a candidate therapeutic target for NSCLC treatment.

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SLC39A4 expression is associated with enhanced cell migration, cisplatin resistance, and poor survival in non-small cell lung cancer

Cited by 30 publications

References 41 publications

PLEK2 mediates metastasis and vascular invasion via the ubiquitin‐dependent degradation of SHIP2 in non‐small cell lung cancer

PLEK2 mediates metastasis and vascular invasion via the ubiquitin‐dependent degradation of SHIP2 in non‐small cell lung cancer

The ZIP6/ZIP10 heteromer is essential for the zinc-mediated trigger of mitosis

Upregulated miR‑665 expression independently predicts poor prognosis of lung cancer and facilitates tumor cell proliferation, migration and invasion

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