Serine-arginine protein kinase 1 promotes a cancer stem cell-like phenotype through activation of Wnt/β-catenin signalling in NSCLC

Gong, Li‐ping; Song, Junwei; Lin, Xi; Wei, Fa-Kai; Zhang, Cuicui; Wang, Zimei; Zhu, Jinrong; Wu, Shu; Chen, Yu; Jin, Liang; Fu, Xiao; Lu, Junqiang; Zhou, Chengyu; Song, Libing

doi:10.1002/path.4767

Cited by 48 publications

(57 citation statements)

References 48 publications

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“…Approach Followed (Testing on Histology Samples/Blood; Data Mining) Level Tested (mRNA; Protein) Clinical Significance Reference Lung data mining; histology samples mRNA; protein ↑SRPK1 was found in NSCLC and was associated with higher tumor stage and shorter survival [29] histology samples mRNA; protein ↑SRPK1 was found in NSCLC [30] data mining mRNA ↑SRPK1 was found in lung adenocarcinoma (a NSCLC histologic type) [31] Breast histology samples mRNA; protein ↑SRPK1 was found in breast cancer and was associated with higher tumor stage and shorter survival [32] histology samples; data mining mRNA; protein ↑SRPK1 was associated with shorter survival in breast cancer and metastatic disease to the lungs and brain [33] data mining mRNA ↑SRPK1 was associated with shorter survival in HER2-negative breast cancer patients treated with chemotherapy [34] histology samples protein ↑SRPK1 was found in breast cancer [35] histology samples protein ↑SRPK1 was found in breast cancer [22] histology samples protein ↑SRPK1 was found in breast cancer and was associated with higher tumor grade [36] Prostate histology samples protein ↑SRPK1 was found in prostate cancer and its precursor (PIN) [26] histology samples protein ↑SRPK1 was found in prostate cancer and was associated with higher stage [37] Colorectal histology samples protein ↑SRPK1 was found in colon cancer and its precursor (adenoma) [22] histology samples protein ↑SRPK1 was found in colon cancer and was associated with higher tumor grade [36] histology samples mRNA; protein ↑SRPK1 was found in colorectal cancer and was associated with higher tumor stage and shorter survival [38] histology samples mRNA; protein ↑SRPK1 was found in colorectal cancer and was associated with higher tumor stage and shorter survival [39] histology samples mRNA ↑SRPK1 was found in colorectal cancer and its precursor (adenoma) [31] histology samples protein ↑SRPK1 and p-AKT were found in colon cancer [40] Stomach data mining mRNA ↑SRPK1 was found in gastric cancer [31] histology samples protein ↑SRPK1 was found in gastric cancer and was associated with higher tumor stage and shorter survival [41] histology samples protein ↑SRPK1 was found in gastric cancer [42] histology samples mRNA; protein ↑SRPK1 was found in gastric cancer and was associated with higher tumor stage and shorter survival [43] Liver histology samples mRNA; protein ↑SRPK1 was associated with higher stage and shorter survival; SRPK1 expression was inversely correlated with miR-1296 expression…”

Section: Cancer Type (Primary Location)mentioning

confidence: 99%

Serine-Arginine Protein Kinase 1 (SRPK1) as a Prognostic Factor and Potential Therapeutic Target in Cancer: Current Evidence and Future Perspectives

Nikas

Themistocleous

Paschou

et al. 2019

Cells

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Cancer, a heterogeneous disease composed of tumor cells and microenvironment, is driven by deregulated processes such as increased proliferation, invasion, metastasis, angiogenesis, and evasion of apoptosis. Alternative splicing, a mechanism led by splicing factors, is implicated in carcinogenesis by affecting any of the processes above. Accumulating evidence suggests that serine-arginine protein kinase 1 (SRPK1), an enzyme that phosphorylates splicing factors rich in serine/arginine domains, has a prognostic and potential predictive role in various cancers. Its upregulation is correlated with higher tumor staging, grading, and shorter survival. SRPK1 is also highly expressed in the premalignant changes of some cancers, showing a potential role in the early steps of carcinogenesis. Of interest, its downregulation in preclinical models has mostly been tumor-suppressive and affected diverse processes heterogeneously, depending on the oncogenic context. In addition, targeting SRPK1 has enhanced sensitivity to platinum-based chemotherapy in some cancers. Lastly, its aberrant function has been noted not only in cancer cells but also in the endothelial cells of the microenvironment. Although the aforementioned evidence seems promising, more studies are needed to reinforce the use of SRPK1 inhibitors in clinical trials. major area of research in the field of intratumor heterogeneity, while their presence is associated with cancer recurrence, metastasis, and resistance to chemotherapy [7].Cancer prognosis depends on multiple factors that affect survival. Tumor staging, traditionally performed with the TNM system, is the most important prognostic factor. It refers to the size of the tumor (T), also the extent of its spread to the regional lymph nodes (N) or distant metastatic sites (M) [8,9]. Grading refers to the histologic picture of the tumor, more specifically, how closely it looks compared to the normal tissue it derives from (differentiation) [10,11]. Both the presence of distant metastases (e.g., in lungs, brain, liver, bones) and poor differentiation are associated with a dismal prognosis [9,11]. The molecular subtype of specific cancers is also critical for cancer survival. For instance, breast cancer has diverse intrinsic subtypes-luminal A and B, human epidermal growth factor receptor 2-enriched (HER2-enriched), and basal-like-that directly impact prognosis [12][13][14]. Luminal breast cancers are most commonly hormone-positive, overexpressing estrogen receptors (ER), and are associated with a better prognosis than HER2-enriched or basal-like breast cancers (BLBCs) [12][13][14][15]. BLBCs, which most commonly present with a triple-negative phenotype, have been linked with the worst prognosis and highest metastatic potential of all breast cancer molecular subtypes [13,16,17].Alternative splicing is the process that removes introns and adds exons in various combinations resulting in multiple mRNA products hence protein transcripts. As a result, it maintains the protein diversity and cellular homeostasis [18]. The...

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Section: Cancer Type (Primary Location)mentioning

confidence: 99%

Serine-Arginine Protein Kinase 1 (SRPK1) as a Prognostic Factor and Potential Therapeutic Target in Cancer: Current Evidence and Future Perspectives

Nikas

Themistocleous

Paschou

et al. 2019

Cells

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show abstract

“…For example, the splicing factor serine-arginine protein kinase 1 (SRPK1) has been reported to stimulate a stem cell-like phenotype in human NSCLC [12] . Gong et al found that SRPK-transduced cells expressed higher levels of pluripotency-associated markers and greater self-renewal capacity [12] . Further they performed gene knockdown experiment to suppress expression of SRPK and demonstrated the converse effect.…”

Section: Research Highlightmentioning

confidence: 99%

Roles of alternative splicing in the pathogenesis of lung cancer

2017

Can Cell Microenviron

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Alternative splicing contributes to the vast complexity of mRNA transcripts and protein isoforms. It has been estimated that the majority of protein-coding genes are subject to alternative splicing in humans. Alternative splicing plays a critical role in physiological processes and cell development programs, and dysregulation of alternative splicing is often associated with pathologic conditions such as cancer. Indeed, the abnormal splicing is frequently found in lung cancer, which produces various protein isoforms with properties that may have different functions and therefore even diverse effects on tumor malignant development. In this highlight, we summarize the evidence supporting the functional role of alternative splicing in lung cancer, discuss the regulation of alternative splicing, and highlight the relevance of splicing variation on lung cancer therapy.

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“…These events could explain rapid tumor relapse and a poor prognosis in cancer patients . Several signaling pathways, such as Sonic Hedgehog, Wnt/β‐catenin, EGFR and SOX2, have been described to regulate the behavior of CSCs and EMT, and contribute to the development of several cancers, such as lung cancer …”

Section: Introductionmentioning

confidence: 99%

“…6 These events could explain rapid tumor relapse and a poor prognosis in cancer patients. 7,8 Several signaling pathways, such as Sonic Hedgehog, 9 Wnt/β-catenin, 10 EGFR 11 and SOX2, 12 have been described to regulate the behavior of CSCs and EMT, and contribute to the development of several cancers, such as lung cancer. 9 EGFR is a receptor tyrosine kinase (RTK) that is stimulated by its ligands such as EGF, amphiregulin, betacellulin, epiregulin, neuregulin, heparin-binding EGF, and transforming growth factor alpha (TGF-α).…”

Section: Introductionmentioning

confidence: 99%

Interferon‐induced transmembrane protein 1‐mediated EGFR/SOX2 signaling axis is essential for progression of non‐small cell lung cancer

Yang

Koh

Sari

et al. 2018

Intl Journal of Cancer

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Emerging data indicate that interferon‐induced transmembrane protein 1 (IFITM1) plays an important role in many cancers. However, it remains unclear whether IFITM1 is functionally indispensable in nonsmall cell lung cancer (NSCLC). Here, using NSCLC cell lines and patient‐derived samples, we show that IFITM1 is essentially required for the progression of NSCLC in vitro and in vivo . Specifically, IFITM1 depletion resulted in a significant reduction in sphere formation, migration, and invasion of NSCLC cells in vitro ; these events were inversely correlated with the ectopic expression of IFITM1. In addition, tumor development was significantly impaired in the absence of IFITM1 in vivo . Mechanistically, epidermal growth factor receptor/sex‐determining region Y‐box 2 (EGFR/SOX2) signaling axis was compromised in the absence of IFITM1, and the ectopic expression of SOX2 partially rescued the defects caused by IFITM1 depletion. More importantly, using 226 patient‐derived samples, we demonstrate that a high level of IFITM1 expression is associated with a poor overall survival (OS) rate in adenocarcinoma but not in squamous cell carcinoma. Collectively, these data suggest that IFITM1 is a poor prognostic marker of adenocarcinoma and an attractive target to develop novel therapeutics for NSCLC.

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Serine-arginine protein kinase 1 promotes a cancer stem cell-like phenotype through activation of Wnt/β-catenin signalling in NSCLC

Cited by 48 publications

References 48 publications

Serine-Arginine Protein Kinase 1 (SRPK1) as a Prognostic Factor and Potential Therapeutic Target in Cancer: Current Evidence and Future Perspectives

Serine-Arginine Protein Kinase 1 (SRPK1) as a Prognostic Factor and Potential Therapeutic Target in Cancer: Current Evidence and Future Perspectives

Roles of alternative splicing in the pathogenesis of lung cancer

Interferon‐induced transmembrane protein 1‐mediated EGFR/SOX2 signaling axis is essential for progression of non‐small cell lung cancer

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