Cluster of differentiation 44 (CD44), a marker for cancer stem cells, has been reported to be associated with poor prognosis in non‑small cell lung cancer (NSCLC), but its involvement in tumor growth has not fully been elucidated. The present study explored the associations between CD44 expression and clinicopathological features using immunohistochemistry in 94 NSCLC cases, as well as proliferation in cells with aberrant expression of this protein. Overexpression of CD44 was achieved by transfecting H1299 cells with CD44 expression vectors, and inhibition of CD44 expression was performed by transfecting small interfering RNAs into A549 cells. Cell proliferation was measured using Cell Counting Kit‑8 assays and flat plate colony formation assay was performed to confirm the cellular anchorage growth in vitro. In total, 64 (68.1%) of the 94 NSCLC cases stained positive for CD44 expression. High expression of CD44 was associated with advanced T stage in NSCLC. Overexpression of CD44 in H1299 cells promoted cell proliferation and colony formation in vitro. Meanwhile, knockdown of CD44 expression in A549 cells suppressed cell proliferation and colony formation in vitro. High expression of CD44 may promote NSCLC progression by increasing cancer cell proliferation; therefore, it may serve as a potential biomarker for diagnosis or target therapy.

Elevated IgG expression in cancer cells has been implicated in exacerbated malignancy and poor clinical prognosis. Accumulating evidence indicates that a nonconventional sialylation modification is critical for the function of cancer-derived IgG, indicating the need for a better understanding of the regulatory mechanisms that control the expression and function of sialylated cancer IgG (SIA-cIgG). Here, we conducted genome-wide CRISPR activation screening and identified OCT4 and SOX2 as the key factors that promote SIA-cIgG expression. Functional investigation revealed that SIA-cIgG reciprocally stimulated SOX2 by activating the c-Met/Akt/Erk signaling axis, constituting a self-propagating loop of SIA-cIgG/c-Met/SOX2/SIA-cIgG signaling. This signaling loop was highly active in stem-like cells from many epithelial cancers and was crucial for cancer stemness in vitro and in vivo. Notably, the mAb RP215, which specifically recognizes the Asn162 sialylation–related epitope on SIA-cIgG, effectively blocked the SIA-cIgG–driven signaling loop. Furthermore, RP215 significantly inhibited lung cancer cell stemness and tumor growth in a patient-derived xenograft model. In conclusion, these findings revealed a self-propagating c-Met/SOX2/SIA-cIgG signaling loop that promotes cancer stemness, identifying novel therapeutic strategies for cancer treatment. Significance: Sialylated cancer IgG activates c-Met-SOX2 signaling to promote stemness properties in cancer cells and can be targeted to suppress tumor growth.

Circulating microRNA-422a is associated with lymphatic metastasis in lung cancer

Autophagy serves a critical function in the pathogenesis, response to therapy and clinical outcome in cancers. Although a recent report showed a role of iASPP in suppressing autophagy, its potential activity as a regulator of autophagy has not been investigated in lung cancer. Here we investigated the potential function and molecular mechanism of iASPP in mediating autophagy in human non-small-cell lung cancer. Our data suggested that forced expression of iASPP triggered autophagic flux, while inhibition of iASPP suppressed autophagy at the autophagsome formation stage in vitro. Furthermore, in vivo overexpression of iASPP in SCID/NOD mice promoted tumorigenesis and autophagy, with an increase in the conversion from LC3-I to LC3-II. The effects of iASPP were mediated through activation of mTOR pathway. Finally, cytoplasmic iASPP expression was upregulated in lung cancer patients, and was identified as an independent poor prognostic factor for lung cancer-specific death in patient samples. Taken together, our data showed that iASPP could promote tumor growth by increasing autophagic flux, and iASPP could serve as a poor prognostic factor and a potential therapeutic target in lung cancer.

Background: It is clearly necessary to discover prognostic biomarkers to identify stage I patients at risk of recurrence and give them timely postoperative treatment. Materials and methods: Data of stage I lung adenocarcinoma were retrieved from four gene series in Gene Expression Omnibus (GEO) database (GS E50081, GSE30219, GSE37745, and GSE13213). Partek Genomics Suite software was used to identify survival-related genes for finding candidate indicators for early-stage patients at risk of recurrence. Differential expression of MTBP (MDM2 binding protein) in early-stage lung adenocarcinoma tissues was determined by immunohistochemical staining. The effects of MTBP interference expression and overexpression on viability, migration, and invasion capacity of lung cells were evaluated using Cell Counting Kit-8, wound healing, and Transwell assays. The tumor growth and lung metastasis in vivo were observed in chick embryo chorioallantoic membrane model. Human Exon 2.0 ST Array was used to analyze downstream regulation genes of MTBP in lung cancer cells. Involvement of ZEB2 and epithelial mesenchymal transition (EMT) markers was investigated by Western blot. Results: By mining GEO database, we identified MTBP as a poor prognostic indicator of stage I lung adenocarcinomas. In addition, increased expression of MTBP was also associated with poor survival in our early-stage lung adenocarcinoma cohort. Further experiment suggested that knockdown of MTBP suppressed the migration and invasion of A549 and 111975 cells in vitro and in vivo, whereas overexpression of MTBP in HCC827 and PC9 cells promoted the migration and invasion in vitro and in vivo. Furthermore, ZEB2 upregulation directly activated EMT to mediate the downstream effects of MTBP involved in lung cancer cells metastasis. Conclusion: MTBP is an independent indicator for poor prognosis in stage flung adenocarcinomas and might promote the aggressive phenotype of non-small-cell lung cancer by inducing the EMT process through upregulating ZEB2 expression.

This study is to investigate the relationship between ectonucleoside triphosphate diphosphohydrolase 5 (ENTPD5) expression and lung cancer clinicopathological factors, and the impact of ENTPD5 on lung cancer cell functions. Lung cancer specimens and matched adjacent normal tissues were obtained from patients without any preoperative radiotherapy or chemotherapy. Knockdown of ETNPD5 expression led to significantly decreased lung cancer cell growth rate, markedly increased apoptosis and the ability to repair, and significantly reduced invasion. Gene chip tests showed that knockdown of ENTPD5 expression caused more Caspase expression. Quantitative real-time polymerase chain reaction showed that the Caspase 3 expression was significantly increased after the knockdown of ENTPD5. In addition, immunohistochemistry showed that the tumor growth marker, proliferating cell nuclear antigen, was significantly reduced in the knockdown model. Tumorigenicity assay and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay showed that the apoptosis of lung cancer cells was increased in the knockdown model. Our results suggest that ENTPD5 affects lung cancer apoptosis via Caspase 3 pathway, and can be potentially used to monitor prognosis or to guide appropriate therapeutic regimens.