Secreted frizzled related protein 3 (SFRP3) contains a cysteine-rich domain (CRD) that shares homology with Frizzled CRD and regulates WNT signaling. Independent studies showed epigenetic silencing of SFRP3 in melanoma and hepatocellular carcinoma. Moreover, a tumor suppressive function of SFRP3 was shown in androgen-independent prostate and gastric cancer cells. The current study is the first to investigate SFRP3 expression and its potential clinical impact on non-small cell lung carcinoma (NSCLC). WNT signaling components present on NSCLC subtypes were preliminary elucidated by expression data of The Cancer Genome Atlas (TCGA). We identified a distinct expression signature of relevant WNT signaling components that differ between adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC). Of interest, canonical WNT signaling is predominant in LUAD samples and non-canonical WNT signaling is predominant in LUSC. In line, high SFRP3 expression resulted in beneficial clinical outcome for LUAD but not for LUSC patients. Furthermore, SFRP3 mRNA expression was significantly decreased in NSCLC tissue compared to normal lung samples. TCGA data verified the reduction of SFRP3 in LUAD and LUSC patients. Moreover, DNA hypermethylation of SFRP3 was evaluated in the TCGA methylation dataset resulting in epigenetic inactivation of SFRP3 expression in LUAD, but not in LUSC, and was validated by pyrosequencing of our NSCLC tissue cohort and in vitro demethylation experiments. Immunohistochemistry confirmed SFRP3 protein downregulation in primary NSCLC and indicated abundant expression in normal lung tissue. Two adenocarcinoma gain-of-function models were used to analyze the functional impact of SFRP3 on cell proliferation and regulation of CyclinD1 expression in vitro.Our results indicate that SFRP3 acts as a novel putative tumor suppressor gene in adenocarcinoma of the lung possibly regulating canonical WNT signaling.
Combinations of text and different types of pictures are commonplace in biology as in science in general. The single representations (i.e., text, picture) constituting a text-picture combination may contain redundant or complementary information. The ability to identify and integrate information in different kinds of text-picture combinations is indispensable for engaging in science and is normatively expected to be acquired in school. In this experimental study, which was not preregistered in an independent institutional registry, N ¼ 240 undergraduate students worked on 2 constructed-response biology tasks originating from authentic final exams to obtain the higher education entrance qualification. The material carried equivalent information between conditions but consisted of redundant or non-redundant text-picture combinations or only texts. Analysis of variance revealed negative effects of the depictive representations on students' performance, but these effects only occurred in 1 of the 2 tasks: Students in the text-only group reached the highest mean score, those who worked with the non-redundant text-picture combinations the lowest mean score. Implications for science education are discussed.
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