Serine peptidase inhibitor Kazal type III (SPINK3) promotes BRL‐3A cell proliferation by targeting the PI3K–AKT signaling pathway

Chang, Cuifang; Xie, Junjie; Yang, Qingdan; Yang, Jing; Luo, Yaru; Xi, Lingling; Guo, Jiuxin; Yang, Ganggang; Jin, Wei; Wang, Gaiping

doi:10.1002/jcp.29130

Cited by 4 publications

(3 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In CRC, metastasis-specific mutations are enhanced in phosphatidylinositol 3-kinase (PI3K)/AKT signaling, cell adhesion, and ECM, implying genetic programming for specific recombination and colonization [ 39 ]. SPINK1 and SPINK3 have been suggested to promote the proliferation of colorectal cancer cells [ 16 ] and rat liver cells [ 40 ], respectively, through the PI3K/AKT signaling pathway. As mentioned previously, whether SPINK4 can downregulate HTRA1 to activate the PI3K/AKT pathway involved in rectal cancer metastasis needs further verification.…”

Section: Discussionmentioning

confidence: 99%

High SPINK4 Expression Predicts Poor Outcomes among Rectal Cancer Patients Receiving CCRT

et al. 2021

View full text Add to dashboard Cite

Background: Patients with rectal cancer can prospectively be favored for neoadjuvant concurrent chemoradiotherapy (CCRT) to downstage before a radical proctectomy, but the risk stratification and clinical outcomes remain disappointing. Methods: From a published rectal cancer transcriptome dataset (GSE35452), we highlighted extracellular matrix (ECM)-linked genes and identified the serine protease inhibitor Kazal-type 4 (SPINK4) gene as the most relevant among the top 10 differentially expressed genes associated with CCRT resistance. We accumulated the cases of 172 rectal cancer patients who received neoadjuvant CCRT followed by surgery and collected tumor specimens for the evaluation of the expression of SPINK4 using immunohistochemistry. Results: The results revealed that high SPINK4 immunoexpression was significantly related to advanced pre-CCRT and post-CCRT tumor status (both p < 0.001), post-CCRT lymph node metastasis (p = 0.001), more vascular and perineurial invasion (p = 0.015 and p = 0.023), and a lower degree of tumor regression (p = 0.001). In univariate analyses, high SPINK4 immunoexpression was remarkably correlated with worse disease-specific survival (DSS) (p < 0.0001), local recurrence-free survival (LRFS) (p = 0.0017), and metastasis-free survival (MeFS) (p < 0.0001). Furthermore, in multivariate analyses, high SPINK4 immunoexpression remained independently prognostic of inferior DSS and MeFS (p = 0.004 and p = 0.002). Conclusion: These results imply that high SPINK4 expression is associated with advanced clinicopathological features and a poor therapeutic response among rectal cancer patients undergoing CCRT, thus validating the prospective prognostic value of SPINK4 for those patients.

show abstract

Section: Discussionmentioning

confidence: 99%

High SPINK4 Expression Predicts Poor Outcomes among Rectal Cancer Patients Receiving CCRT

et al. 2021

View full text Add to dashboard Cite

show abstract

“…We also discussed the possibility that SPINK9 can affect tumors by inhibiting KLK5. In addition, SPINK3 can also inhibit KLKs (214) and activate PI3K/ AKT by enhancing the expression of AKT1 to promote the proliferation of normal liver cells (215). Therefore, SPINK3 and SPINK9 have potential biological significance in tumors.…”

Section: Discussionmentioning

confidence: 99%

SPINKs in Tumors: Potential Therapeutic Targets

Liao

Wang

et al. 2022

Front. Oncol.

View full text Add to dashboard Cite

The serine protease inhibitor Kazal type (SPINK) family includes SPINK1-14 and is the largest branch in the serine protease inhibitor family. SPINKs play an important role in pancreatic physiology and disease, sperm maturation and capacitation, Nager syndrome, inflammation and the skin barrier. Evidence shows that the unregulated expression of SPINK1, 2, 4, 5, 6, 7, and 13 is closely related to human tumors. Different SPINKs exhibit various regulatory modes in different tumors and can be used as tumor prognostic markers. This article reviews the role of SPINK1, 2, 4, 5, 6, 7, and 13 in different human cancer processes and helps to identify new cancer treatment targets.

show abstract

“…The aKT/erK signaling pathway is one of the most important cellular signaling pathways for cell proliferation and it has been reported to serve an important role in the occurrence and development of Hcc (40), colorectal cancer (41) and ovarian cancer (42). The aKT/erK signaling pathway has been identified to not only activate downstream signaling molecules, but also interact with other signaling molecules and result in a cascade activation (43,44). However, it is not clear whether Fer1l4 also affects the biological phenotype of cell proliferation, migration, invasion and apoptosis by mediating the aKT/erK signaling pathway in lScc.…”

Section: Discussionmentioning

confidence: 99%

Long non‑coding RNA fer‑1‑like family member 4 serves as a tumor suppressor in laryngeal squamous cell carcinoma cells via regulating the AKT/ERK signaling pathway

Jiao

Liu

et al. 2020

Mol Med Rep

View full text Add to dashboard Cite

laryngeal squamous cell carcinoma (lScc) is a common type of malignant tumor of the head and neck. an increasing number of studies have illustrated that long non-coding rnas (lncrnas) serve an important role in the occurrence and development of lScc. Therefore, the present study aimed to investigate the expression changes and mechanism of lncrna fer-1-like family member 4 (Fer1l4) in the progression of lScc. The expression levels of Fer1l4 in lScc cell lines (aMc-Hn-8, Tu 686, M4e and M2e) and a normal cell line (HBe135-e6e7) were analyzed using reverse transcription-quantitative Pcr. The Fer1l4 overexpression plasmid (plasmid-Fer1l4) was subsequently transfected into Tu 686 cells to upregulate the expression levels of Fer1l4. cell viability was detected using a cell counting Kit-8 assay, cell proliferation was analyzed using a colony formation assay, apoptosis was examined by flow cytometry, and cell migration and invasion were determined using wound healing and Transwell assays, respectively. in addition, the plasmid-Fer1l4 cells were also treated with insulin-like growth factor 1 (iGF-1) to determine the effect of Fer1l4 on the aKT/erK signaling pathway, and the effect of the plasmid-Fer1l4 on the expression levels of aKT/erK signaling pathway-related proteins were analyzed using western blotting. The results of the present study revealed that Fer1l4 expression levels were downregulated in aMc-Hn-8 and Tu 686 cells. Notably, FER1L overexpression significantly reduced the cell viability, proliferation, migration and invasion of lScc cells, while promoting apoptosis. Meanwhile, the plasmid-FER1L4 also significantly suppressed the phosphorylation levels of aKT and erK. Further studies indicated that the aforementioned changes could be reversed by iGF-1, indicating Fer1l4 may regulate the progression of lScc cells by inhibiting the aKT/erK signaling pathway. in conclusion, the present study provided a potential novel direction for the treatment of lScc in the future and suggested that Fer1l4 may be a new target in this field.

show abstract

Serine peptidase inhibitor Kazal type III (SPINK3) promotes BRL‐3A cell proliferation by targeting the PI3K–AKT signaling pathway

Cited by 4 publications

References 19 publications

High SPINK4 Expression Predicts Poor Outcomes among Rectal Cancer Patients Receiving CCRT

High SPINK4 Expression Predicts Poor Outcomes among Rectal Cancer Patients Receiving CCRT

SPINKs in Tumors: Potential Therapeutic Targets

Long non‑coding RNA fer‑1‑like family member 4 serves as a tumor suppressor in laryngeal squamous cell carcinoma cells via regulating the AKT/ERK signaling pathway

Contact Info

Product

Resources

About