PLS3 predicts poor prognosis in pancreatic cancer and promotes cancer cell proliferation via PI3K/AKT signaling

Xin, Zechang; Li, Duguang; Mao, Feiyu; Du, Yuchen; Wang, Xiaodong; Xu, Peng; Li, Zhennan; Qian, Jianjun; Yao, Jie

doi:10.1002/jcp.29685

Cited by 14 publications

(15 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…PLS3 interacts with NFκB repressing factor (NKRF) facilitating its translocation into the nucleus, and thus the transcription of nuclear factor-activated T cells c1 (NFATC1) and an important factor in osteoclastogenesis [16]. Through the PI3K/AKT signaling pathway, PLS3 regulates tumor progression by promoting the proliferation and migration of cancer cells [75].…”

Section: Signalingmentioning

confidence: 99%

See 1 more Smart Citation

Plastin 3 in health and disease: a matter of balance

Wolff

Strathmann

Müller

et al. 2021

Cell. Mol. Life Sci.

View full text Add to dashboard Cite

For a long time, PLS3 (plastin 3, also known as T-plastin or fimbrin) has been considered a rather inconspicuous protein, involved in F-actin-binding and -bundling. However, in recent years, a plethora of discoveries have turned PLS3 into a highly interesting protein involved in many cellular processes, signaling pathways, and diseases. PLS3 is localized on the X-chromosome, but shows sex-specific, inter-individual and tissue-specific expression variability pointing towards skewed X-inactivation. PLS3 is expressed in all solid tissues but usually not in hematopoietic cells. When escaping X-inactivation, PLS3 triggers a plethora of different types of cancers. Elevated PLS3 levels are considered a prognostic biomarker for cancer and refractory response to therapies. When it is knocked out or mutated in humans and mice, it causes osteoporosis with bone fractures; it is the only protein involved in actin dynamics responsible for osteoporosis. Instead, when PLS3 is upregulated, it acts as a highly protective SMN-independent modifier in spinal muscular atrophy (SMA). Here, it seems to counteract reduced F-actin levels by restoring impaired endocytosis and disturbed calcium homeostasis caused by reduced SMN levels. In contrast, an upregulation of PLS3 on wild-type level might cause osteoarthritis. This emphasizes that the amount of PLS3 in our cells must be precisely balanced; both too much and too little can be detrimental. Actin-dynamics, regulated by PLS3 among others, are crucial in a lot of cellular processes including endocytosis, cell migration, axonal growth, neurotransmission, translation, and others. Also, PLS3 levels influence the infection with different bacteria, mycosis, and other pathogens.

show abstract

Section: Signalingmentioning

confidence: 99%

“…High PLS3 expression is also a feature of pancreatic cancer cells. Here, PLS3 acts as an oncogene and its overexpression triggers the activation of the PI3K/ AKT signaling pathway leading to cancer progression [75]. In non-small-cell lung cancer (NSCLC), increased PLS3 plasma levels are a predictor of poor survival.…”

Section: Malignancies In Solid Tissuesmentioning

confidence: 99%

Plastin 3 in health and disease: a matter of balance

Wolff

Strathmann

Müller

et al. 2021

Cell. Mol. Life Sci.

View full text Add to dashboard Cite

show abstract

“…Regarding PLS3, one recent study that included 207 PDA tissue specimens showed that the overexpression of PLS3 was associated with tumor stage and pathology as well as poor OS in PDA patients. PLS3 was an independent prognostic factor in PDA patients [ 14 ]. The authors’ in vitro data demonstrated that PLS3 expression induced PDA cell proliferation and invasion, which were associated with increased PI3K/AKT activity in PDA cells [ 14 ].…”

Section: Discussionmentioning

confidence: 99%

Plastin-3 is a diagnostic and prognostic marker for pancreatic adenocarcinoma and distinguishes from diffuse large B-cell lymphoma

Xiong

Wang

et al. 2021

Cancer Cell Int

View full text Add to dashboard Cite

Background Altered Plastin-3 (PLS3; an actin-binding protein) expression was associated with human carcinogenesis, including pancreatic ductal adenocarcinoma (PDA). This study first assessed differentially expressed genes (DEGs) and then bioinformatically and experimentally confirmed PLS3 to be able to predict PDA prognosis and distinguish PDA from diffuse large B-cell lymphoma. Methods This study screened multiple online databases and revealed DEGs among PDA, normal pancreas, diffuse large B-cell lymphoma (DLBCL), and normal lymph node tissues and then focused on PLS3. These DEGs were analyzed for Gene Ontology (GO) terms, Kaplan–Meier curves, and the log-rank test to characterize their association with PDA prognosis. The receiver operating characteristic curve (ROC) was plotted, and Spearman’s tests were performed. Differential PLS3 expression in different tissue specimens (n = 30) was evaluated by reverse transcription quantitative polymerase chain reaction (RT-qPCR). Results There were a great number of DEGs between PDA and lymph node, between PDA and DLBCL, and between PDA and normal pancreatic tissues. Five DEGs (NET1, KCNK1, MAL2, PLS1, and PLS3) were associated with poor overall survival of PDA patients, but only PLS3 was further verified by the R2 and ICGC datasets. The ROC analysis showed a high PLS3 AUC (area under the curve) value for PDA diagnosis, while PLS3 was able to distinguish PDA from DLBCL. The results of Spearman's analysis showed that PLS3 expression was associated with levels of KRT7, SPP1, and SPARC. Differential PLS3 expression in different tissue specimens was further validated by RT-qPCR. Conclusions Altered PLS3 expression was useful in diagnosis and prognosis of PDA as well as to distinguish PDA from DLBCL.

show abstract

“…PLS3, also known as T-plastin, is an actin binding protein and not a classical organic anion transporter [ 32 ]. High PLS3 expression has been shown to have poor prognosis in pancreatic cancer, acute myeloid leukemia, gastric cancer, and colorectal cancer [ 33 , 34 , 35 , 36 ]. A direct function of PLS3 as transport protein is not known in the analyzed cancer entities.…”

Section: Discussionmentioning

confidence: 99%

Identification of Prognostic Organic Cation and Anion Transporters in Different Cancer Entities by In Silico Analysis

Edemir

2020

IJMS

View full text Add to dashboard Cite

The information derived from next generation sequencing technology allows the identification of deregulated genes, gene mutations, epigenetic modifications, and other genomic events that are associated with a given tumor entity. Its combination with clinical data allows the prediction of patients’ survival with a specific gene expression pattern. Organic anion transporters and organic cation transporters are important proteins that transport a variety of substances across membranes. They are also able to transport drugs that are used for the treatment of cancer and could be used to improve treatment. In this study, we have made use of publicly available data to analyze if the expression of organic anion transporters or organic cation transporters have a prognostic value for a given tumor entity. The expression of most organic cation transporters is prognostic favorable. Within the organic anion transporters, the ratio between favorable and unfavorable organic anion transporters is nearly equal for most tumor entities and only in liver cancer is the number of unfavorable genes two times higher compared to favorable genes. Within the favorable genes, UNC13B, and SFXN2 cover nine cancer types and in the same way, SLC2A1, PLS3, SLC16A1, and SLC16A3 within the unfavorable set of genes and could serve as novel target structures.

show abstract

PLS3 predicts poor prognosis in pancreatic cancer and promotes cancer cell proliferation via PI3K/AKT signaling

Cited by 14 publications

References 24 publications

Plastin 3 in health and disease: a matter of balance

Plastin 3 in health and disease: a matter of balance

Plastin-3 is a diagnostic and prognostic marker for pancreatic adenocarcinoma and distinguishes from diffuse large B-cell lymphoma

Identification of Prognostic Organic Cation and Anion Transporters in Different Cancer Entities by In Silico Analysis

Contact Info

Product

Resources

About