SPHK1 contributes to cisplatin resistance in bladder cancer cells via the NONO/STAT3 axis

Qin, Zijia; Tong, Hang; Li, Tinghao; Cao, Honghao; Zhu, Junlong; Su, Yin; He, Weiyang

doi:10.3892/ijmm.2021.5037

Cited by 13 publications

(9 citation statements)

References 47 publications

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“…SPHK1 has been reported to activate several cancer-related signaling pathways, such as the TRAF6/ULK1 pathway in colorectal cancer [30], the NONO/STAT3 pathway in bladder cancer [5], and the JAK/mTOR pathway in NSCLC [12]. This study focuses on the NF-κB pathway, and the effects of SPHK1 on other pathways will be further explored in our future studies.…”

Section: Discussionmentioning

confidence: 97%

“…Sphingosine kinase 1 (SPHK1) is a conserved lipid kinase that phosphorylates sphingosine to produce sphingosin-1-phosphate (S1P), which has been found to play various functions at different stages of tumor progression [5]. SPHK1 exists in the cytoplasm, is a key signaling molecule mediating various aspects of cells, and plays a role in a variety of carcinogenic processes, including cell proliferation, migration and invasion [6,7].…”

Section: Introducementioning

confidence: 99%

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SPHK1 promotes the migration and invasion of gastric cancer cells through NF-κB pathway

Ling,

Ji,

Guan

et al. 2024

Preprint

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Background: Gastric cancer (GC) is one of the most common malignant tumors. Sphingosine kinase-1 (SPHK1) is a member of the SPHK family of proteins,which are involved in the pathogenesis of various cancers. This study aimed to investigate SPHK1 expression in GC tissues, and its effects on the migration and invasion of GC cell lines. Methods: Bioinformatics predicted SPHK1 expression and prognosis. The expression of SPHK1 was detected by immunohistochemistry. Real-time PCR analysis was used to detect SPHK1mRNA expression. Cell migration was detected by cell scratch methods. Cell migration and invasion were detected by Transwell assays. Western Blotting was used to detect protein expression. Results: The expression of SPHK1 in GC was significantly higher than that in matched non-cancer tissues. Knockdown of SPHK1 can reduce the migration and invasion of GC cells, while overexpression of SPHK1 has the opposite effect. In addition, SPHK1 positively regulates protein levels of phosphorylated P65(p-P65), as well as protein expression of vascular endothelial growth factor A(VEGFA) and interleukin 17(IL-17) at transcriptional targets of the NF-κB signaling pathway. The blockage of the NF-κB signaling pathway by PDTC could reverse the SPHK1-promoted GC cell migration and invasion. Conclusions: Our results elucidate the key role of SPHK1 in promoting GC cell migration and invasion, and suggest that SPHK1 may be a potential molecular target for preventing GC metastasis.

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Section: Discussionmentioning

confidence: 97%

Section: Introducementioning

confidence: 99%

SPHK1 promotes the migration and invasion of gastric cancer cells through NF-κB pathway

Ling,

Ji,

Guan

et al. 2024

Preprint

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“… 13 Despite various therapeutic strategies for bladder cancer, tumor cells have capacity of developing resistance to therapy. 14 , 15 Therefore, novel modalities for treatment of bladder cancer should be followed. Furthermore, different diagnostic tools including magnetic resonance imaging (MRI), computed tomography (CT) and chest X‐ray, among others are utilized for bladder cancer detection.…”

Section: Introductionmentioning

confidence: 99%

“…There is also a classification of bladder cancer based on the manner of tumor development including squamous cell carcinoma and carcinoma in mucus‐secreting cells of the bladder which indeed is rare 13 . Despite various therapeutic strategies for bladder cancer, tumor cells have capacity of developing resistance to therapy 14,15 . Therefore, novel modalities for treatment of bladder cancer should be followed.…”

Section: Introductionmentioning

confidence: 99%

(Nano)platforms in bladder cancer therapy: Challenges and opportunities

Ashrafizadeh

Zarrabi

Karimi‐Maleh

et al. 2022

Bioengineering & Transla Med

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Urological cancers are among the most common malignancies around the world. In particular, bladder cancer severely threatens human health due to its aggressive and heterogeneous nature. Various therapeutic modalities have been considered for the treatment of bladder cancer although its prognosis remains unfavorable. It is perceived that treatment of bladder cancer depends on an interdisciplinary approach combining biology and engineering. The nanotechnological approaches have been introduced in the treatment of various cancers, especially bladder cancer. The current review aims to emphasize and highlight possible applications of nanomedicine in eradication of bladder tumor. Nanoparticles can improve efficacy of drugs in bladder cancer therapy through elevating their bioavailability. The potential of genetic tools such as siRNA and miRNA in gene expression regulation can be boosted using nanostructures by facilitating their internalization and accumulation at tumor sites and cells. Nanoparticles can provide photodynamic and photothermal therapy for ROS overgeneration and hyperthermia, respectively, in the suppression of bladder cancer. Furthermore, remodeling of tumor microenvironment and infiltration of immune cells for the purpose of immunotherapy are achieved through cargo‐loaded nanocarriers. Nanocarriers are mainly internalized in bladder tumor cells by endocytosis, and proper design of smart nanoparticles such as pH‐, redox‐, and light‐responsive nanocarriers is of importance for targeted tumor therapy. Bladder cancer biomarkers can be detected using nanoparticles for timely diagnosis of patients. Based on their accumulation at the tumor site, they can be employed for tumor imaging. The clinical translation and challenges are also covered in current review.

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“…Masayuki et al demonstrated a critical role for circulating S1P produced by tumors and the SPHK1/S1P/S1PR1 axis in obesity-related inflammation, the formation of lung metastatic niches and breast cancer metastasis [ 11 ]. In bladder cancer, elevated SPHK1 expression was also proved to enhance the chemoresistance to cisplatin and contribute to poor survival rates in patients [ 12 ]. In addition, previous studies have already linked the high expression of SPHK1 with tumor progression and the poor survival of patients with NSCLC [ 13 ], but the molecular mechanism still needs further investigation.…”

Section: Introductionmentioning

confidence: 99%

Targeting SPHK1/PBX1 Axis Induced Cell Cycle Arrest in Non-Small Cell Lung Cancer

Lin

Han

et al. 2022

IJMS

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Non-small cell lung cancer (NSCLC) accounts for 85~90% of lung cancer cases, with a poor prognosis and a low 5-year survival rate. Sphingosine kinase-1 (SPHK1), a key enzyme in regulating sphingolipid metabolism, has been reported to be involved in the development of NSCLC, although the underlying mechanism remains unclear. In the present study, we demonstrated the abnormal signature of SPHK1 in NSCLC lesions and cell lines of lung cancers with a potential tumorigenic role in cell cycle regulation. Functionally, ectopic Pre-B cell leukemia homeobox-1 (PBX1) was capable of restoring the arrested G1 phase induced by SPHK1 knockdown. However, exogenous sphingosine-1-phosphate (S1P) supply had little impact on the cell cycle arrest by PBX1 silence. Furthermore, S1P receptor S1PR3 was revealed as a specific switch to transport the extracellular S1P signal into cells, and subsequently activated PBX1 to regulate cell cycle progression. In addition, Akt signaling partially participated in the SPHK1/S1PR3/PBX1 axis to regulate the cell cycle, and the Akt inhibitor significantly decreased PBX1 expression and induced G1 arrest. Targeting SPHK1 with PF-543 significantly inhibited the cell cycle and tumor growth in preclinical xenograft tumor models of NSCLC. Taken together, our findings exhibit the vital role of the SPHK1/S1PR3/PBX1 axis in regulating the cell cycle of NSCLC, and targeting SPHK1 may develop a therapeutic effect in tumor treatment.

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SPHK1 contributes to cisplatin resistance in bladder cancer cells via the NONO/STAT3 axis

Cited by 13 publications

References 47 publications

SPHK1 promotes the migration and invasion of gastric cancer cells through NF-κB pathway

SPHK1 promotes the migration and invasion of gastric cancer cells through NF-κB pathway

(Nano)platforms in bladder cancer therapy: Challenges and opportunities

Targeting SPHK1/PBX1 Axis Induced Cell Cycle Arrest in Non-Small Cell Lung Cancer

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