Serine protease inhibitor Kazal type 1 promotes epithelial-mesenchymal transition through EGFR signaling pathway in prostate cancer

Wang, Chunni; Wang, Lin; Su, Bo; Lü, Ning; Song, Jingjing; Yang, Xiaoqing; Fu, Weiwei; Tan, Wenyong; Han, Bo

doi:10.1002/pros.22787

Cited by 45 publications

(31 citation statements)

References 56 publications

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“…Later, Leinonen et al [20] reported that SPINK1 expression is associated with aggressive form of the disease and could serve as a biomarker in endocrine-treated PCa patients. In consistent with these findings, our results revealed that SPINK1 overexpression is an unfavorable prognostic factor in Chinese PCa patients [21].…”

Section: Prognostic Association Of Spink1 Overexpressionsupporting

confidence: 90%

“…these studies, we also suggested SPINK1 is mutually exclusive with ERG rearrangement status in Chinese PCa patients and the prevalence of SPINK1 overexpression is comparable with that of western populations [21]. In contrast, some previous reports did not find such mutual exclusivity, although the majority of which suggested the incidence rate was very low for concomitance of SPINK1 and ETS fusions [20,22].…”

Section: Introductionsupporting

confidence: 60%

“…Ateeq et al [25] proposed that SPINK1 functions at least in part to stimulate EGFR signaling in an autocrine loop. Clinically, the notion of SPINK1-EGFR axis was evidenced by the significant co-overexpression of SPINK1 and EGFR in PCa patients cohort [21]. Most recently, we reported that SPINK1 induces epitheial mesenchymal transition (EMT) in PCa via activating EGFR, leading to increased migratory and invasive capacity in vitro [21].…”

Section: Introductionmentioning

confidence: 99%

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Roles of Serine Protease Inhibitor Kazal type 1 (SPINK1) in Prostate Cancer

Shen¹,

Zhang²,

Qi³

et al. 2014

Med chem

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Section: Prognostic Association Of Spink1 Overexpressionsupporting

confidence: 90%

Section: Introductionsupporting

confidence: 60%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Roles of Serine Protease Inhibitor Kazal type 1 (SPINK1) in Prostate Cancer

Shen¹,

Zhang²,

Qi³

et al. 2014

Med chem

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“…A more recent study conducted with RWPE cells showed that SPINK1-induced increase in motility was associated with epithelial-mesenchymal transition (EMT) (36 ). Correlating with the results from pancreatic cancer studies, EGFR and MAPK inhibitors were able to reverse the invasive capacity of prostate cancer cells, suggesting that SPINK1-induced EMT was mediated by the EGFR-MAPK signaling pathway (36 ).…”

Section: Prostate Cancermentioning

confidence: 93%

“…A majority of the oncogenic functions of SPINK1 seem to be mediated by the MAPK pathway (27,36,59,66 ). Current US Food and Drug Administration-approved targeted therapies include the RAF inhibitor sorafenib for treatment of kidney, liver, and thyroid cancer; the MEK inhibitor trametinib for treatment of melanoma; and the EGFR, ERK1/2, and Akt inhibitor lapatinib for treatment of breast cancer.…”

Section: Potential Use Of Spink1 As a Therapeutic Target In Cancermentioning

confidence: 99%

Emerging Roles of SPINK1 in Cancer

et al. 2016

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BACKGROUND Tumor-associated trypsin inhibitor (TATI) was originally isolated from the urine of a patient with ovarian cancer. It was later shown to be produced by many other tumors and several normal tissues. It had earlier been isolated from the pancreas and was hence called pancreatic secretory trypsin inhibitor (PSTI). It belongs to a family of protease inhibitors presently called serine peptidase inhibitor Kazal type (SPINK). In the SPINK family TATI/PSTI is SPINK1, which is the name used in this review. CONTENT In addition to being a protease inhibitor, SPINK1 also acts as an acute-phase reactant and a growth factor. Furthermore, it has been shown to modulate apoptosis. Overexpression of SPINK1 predicts an unfavorable outcome in several cancers and determination of SPINK1 in serum can be used to identify patients at increased risk of aggressive disease. Thus serum SPINK1 can be used as a prognostic tumor marker. Because SPINK1 acts as a growth factor and an inhibitor of apoptosis in some cancers, it has also been suggested that it can be a therapeutic target in cancer. However, because SPINK1 is the major physiological inhibitor of trypsin, inhibition of SPINK1 may increase the risk of pancreatitis. SUMMARY Taking into account the many functions of SPINK1, assessing the role of SPINK1 in cancer has several potentially important clinical applications ranging from a biomarker to a potential new target for cancer therapy.

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TMPRSS2‐ERG gene fusion is rare compared to PTEN deletions in stage T1a prostate cancer

Fisher

Zhang

Wang

et al. 2016

Molecular Carcinogenesis

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T1a prostate cancers (cancer found incidentally in transurethral resection, <5% of the tissue) are indolent tumors of the transition zone. The overexpression of ERG and the inactivation of PTEN have been shown to be important drivers of carcinogenesis in large series of prostate cancer, but the genetics of transition zone tumors have not been well characterized. We evaluated the status of ERG and PTEN in formalin-fixed paraffin-embedded tissue using immunohistochemical and FISH analysis in 54 T1a transition zone tumors. The protein expression of ERG was determined using a rabbit monoclonal antibody and nuclear staining was scored as positive or negative. The genomic status of ERG was determined using 3 colored FISH using an ERG-TMPRSS2 tri-color probe set. The protein expression of PTEN was determined using a rabbit monoclonal antibody and cytoplasmic and nuclear staining was scored as positive or negative. The genomic status of PTEN was determined using dual color FISH with a PTEN probe and a CEP10 probe. We found ERG rearrangement in 2 of 54 tumors (4%), one with protein overexpression by immunohistochemistry. PTEN inactivation was seen in 13 of 54 tumors (24%). Nine of the 13 PTEN alleles were inactivated by hemizygous deletion. No homozygous PTEN deletion was observed. PTEN deletion and ERG rearrangement were mutually exclusive. ERG rearrangement was rare compared to peripheral zone tumors and to PTEN inactivation in T1a transition zone tumors.

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Serine protease inhibitor Kazal type 1 promotes epithelial-mesenchymal transition through EGFR signaling pathway in prostate cancer

Abstract: These findings suggest that SPINK1 promotes EMT through EGFR signaling pathway in PCa and SPINK1 could be a new prognostic marker in Chinese PCas.

Cited by 45 publications

References 56 publications

Roles of Serine Protease Inhibitor Kazal type 1 (SPINK1) in Prostate Cancer

Roles of Serine Protease Inhibitor Kazal type 1 (SPINK1) in Prostate Cancer

Emerging Roles of SPINK1 in Cancer

TMPRSS2‐ERG gene fusion is rare compared to PTEN deletions in stage T1a prostate cancer

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