Targeting S100P Inhibits Colon Cancer Growth and Metastasis by Lentivirus-Mediated RNA Interference and Proteomic Analysis

Jiang, Lei; Lai, Yiu‐Kay; Zhang, Jinfang; Wang, Hua; Lin, Marie C.M.; He, Ming; Kung, Hsiang‐Fu

doi:10.2119/molmed.2011.00008

Cited by 61 publications

(46 citation statements)

References 31 publications

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“…129); and in breast and cervical cancer by glucocorticoids 130 . Consistent with the observation that S100P enhances the migratory capabilities of tumour cells in vitro 131 and metastasis in vivo 132–134 , the majority of S100P targets are cytoskeletal regulators. S100P–mediated activation of ezrin 135 (a membrane–cytoskeleton linker protein) and Ras GTPase-activating-like protein 1 (IQGAP1; a juxtamembrane scaffolding protein that links plasma membrane receptors with downstream signalling pathways) 136 provides a direct mechanism for the regulation of tumour cell migration by S100P.…”

Section: S100 Signalling In Cancer Biologysupporting

confidence: 81%

S100 proteins in cancer

2015

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In humans, the S100 protein family is composed of 21 members that exhibit a high degree of structural similarity, but are not functionally interchangeable. This family of proteins modulates cellular responses by functioning both as intracellular Ca2+ sensors and as extracellular factors. Dysregulated expression of multiple members of the S100 family is a common feature of human cancers, with each type of cancer showing a unique S100 protein profile or signature. Emerging in vivo evidence indicates that the biology of most S100 proteins is complex and multifactorial, and that these proteins actively contribute to tumorigenic processes such as cell proliferation, metastasis, angiogenesis and immune evasion. Drug discovery efforts have identified leads for inhibiting several S100 family members, and two of the identified inhibitors have progressed to clinical trials in patients with cancer. This Review highlights new findings regarding the role of S100 family members in cancer diagnosis and treatment, the contribution of S100 signalling to tumour biology, and the discovery and development of S100 inhibitors for treating cancer.

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Section: S100 Signalling In Cancer Biologysupporting

confidence: 81%

S100 proteins in cancer

2015

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“…Next, cell growth, colony formation and migratory assays were performed using the transduced (SW480/S100P, DLD-1, LS174T) cells. Similar to LS174T cells, DLD-1 cells express both S100P and miR-155 [22, 48]. Knockdown of miR-155 significantly decreased cell growth (Figure 6A; also see Supplementary Figure 3).…”

Section: Resultsmentioning

confidence: 99%

“…Over expression of S100P is associated to poor prognosis and survival in patients with breast and lung cancer [12, 20]. On the contrary, blockage of S100P inhibits colon cancer growth and metastasis, while also improving mice survival [11, 21, 22]. Our group has previously shown that S100P expression is regulated by the PGE 2 /EP4 signaling through cAMP response element-binding protein (CREB) activation in colon cancer cells [10].…”

Section: Introductionmentioning

confidence: 99%

S100P/RAGE signaling regulates microRNA-155 expression via AP-1 activation in colon cancer

Onyeagucha

Mercado-Pimentel

Hutchison

et al. 2013

Experimental Cell Research

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Accumulating evidence indicates that elevated S100P promotes the pathogenesis of cancers, including colon cancer. S100P exerts its effects by binding to and activating the Receptor for Advance Glycation End-products (RAGE). The effects of up-regulated S100P/RAGE signaling on cell functions are well documented. Despite these observations, little is known about the downstream targets of S100P/RAGE signaling. In the present study, we demonstrated for the first time that activation of RAGE by S100P regulates oncogenic microRNA-155 (miR-155) expression through Activator Protein-1 (AP-1) stimulation in colon cancer cells. Ectopic S100P up-regulated miR-155 levels in human colon cancer cells. Conversely, knockdown of S100P resulted in a decrease in miR-155 levels. Exogenous S100P induced miR-155 expression, but blockage of the RAGE with anti-RAGE antibody suppressed the induction of miR-155 by exogenous S100P. Attenuation of AP-1 activation through pharmacological inhibition of MEK activation or genetic inhibition of c-Jun activation using dominant negative c-Jun (TAM67) suppressed miR-155 induction by exogenous S100P. Also, S100P treatment stimulated the enrichment of c-Fos, an AP-1 family member, at the miR-155 host gene promoter site. Finally, a functional study demonstrated that miR-155 knockdown decreases colon cancer cell growth, motility, and invasion. Altogether, these data demonstrate that the expression of miR-155 is regulated by S100P and is dependent on RAGE activation and stimulation of AP-1.

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“…Several studies have linked S100P expression levels to cell proliferation, invasion and migration in various forms of cancer (28). …”

Section: Discussionmentioning

confidence: 99%

S100P is associated with proliferation and migration in nasopharyngeal carcinoma

et al. 2017

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In the present study, the function of S100 calcium binding protein P (S100P) in the C666-1 nasopharyngeal carcinoma (NPC) cell line was examined. The levels of S100P protein in NPC tissues were analyzed using immunohistochemistry, and small interfering RNA silenced S100P expression in C666-1 cells. Subsequently, cell proliferation, colony formation, migration and wound-healing assays were performed in order to assess whether the knockdown of S100P was able to influence the biological behavior of C666-1 cells. The expression levels of the receptor for advanced glycation end products (RAGE) were analyzed using a western blot following the inhibition of S100P. The immunohistochemistry results revealed that S100P was elevated in expression in 45/78 (57.7%) of patients with NPC, as compared with 5/30 (16.7%) of patients with benign inflammation. The S100P protein levels correlated with the rates of proliferation and migration in C666-1 cells. Additionally, reduced S100P expression levels altered a series of intracellular events, including the downregulation of epidermal growth factor receptor, cluster of differentiation (CD) 44, matrix metalloproteinase (MMP) 2 and MMP9 protein expression. In addition, RAGE expression was downregulated in the S100P silenced C666-1 cells, as detected by western blot analysis. These data suggest that S100P is important during the development and progression of nasopharyngeal cancer. Therefore, S100P may provide a novel treatment target for NPC.

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Targeting S100P Inhibits Colon Cancer Growth and Metastasis by Lentivirus-Mediated RNA Interference and Proteomic Analysis

Cited by 61 publications

References 31 publications

S100 proteins in cancer

S100 proteins in cancer

S100P/RAGE signaling regulates microRNA-155 expression via AP-1 activation in colon cancer

S100P is associated with proliferation and migration in nasopharyngeal carcinoma

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