Invasion and intrahepatic metastasis are major factors of poor prognosis in patients with hepatocellular carcinoma (HCC). In this study, we show that increased Src homolog and collagen homolog 3 (Shc3) expression in malignant HCC cell lines associate with HCC invasion and metastasis. Shc3 (N-Shc) was significantly upregulated in tumors of 33 HCC patient samples as compared with adjacent normal tissues. Further analysis of 52 HCC patient samples showed that Shc3 expression correlated with microvascular invasion, cancer staging, and poor prognosis. Shc3 interacted with major vault protein, resulting in activation of MEK1/2 and ERK1/2 independently of Shc1 and c-Raf; this interaction consequently induced epithelial-mesenchymal transition and promoted HCC cell proliferation and metastasis. The observed increase in Shc3 levels was due to demethylation of its upstream promoter, which allowed c-Jun binding. In turn, Shc3 expression promoted c-Jun phosphorylation in a positive feedback loop. Analysis of metastasis using a tumor xenograft mouse model further confirmed the role of Shc3 Taken together, our results indicate the importance of Shc3 in HCC progression and identify Shc3 as a novel biomarker and potential therapeutic target in HCC. Ectopic expression of Shc3 forms a complex with MVP/MEK/ERK to potentiate ERK activation and plays an important role in sorafinib resistance in HCC. .

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s Glycine decarboxylase (GLDC) belongs to the glycine cleavage system and is involved in one-carbon metabolism. We previously reported that GLDC downregulation enhances hepatocellular carcinoma (HCC) progression and intrahepatic metastasis through decreasing ROS-mediated ubiquitination of cofilin. The role of autophagy in cancer metastasis is still controversial. Redox-dependent autophagy largely relies on the magnitude and the rate of ROS generation. Thus, we aimed to explore the role of GLDC in cellular autophagy during HCC progression. We showed that a high GLDC expression level is associated with better overall survival and is an independent factor for the favorable prognosis of HCC patients. GLDC overexpression significantly induced cell autophagy, whereas GLDC downregulation reduced cell autophagy. Of note, GLDC is the post-transcriptional target of miR-30d-5p. GLDC overexpression could rescue miR-30d-5p-mediated cell metastasis and increase autophagy. Furthermore, upregulation of GLDC could significantly decrease p62 expression and impair intrahepatic metastasis in vivo. Taken together, our results suggest that GLDC may play an important role to increasing miR-30d-5p-reduced autophagy to suppress HCC progress.

Long non-coding RNAs (lncRNAs) are defined as transcripts longer than 200 nucleotides with little or no protein-coding capacity. Previously, they were considered transcription byproducts without biological functions. Further studies have shown that lncRNAs are involved in multiple biological and pathological processes, including regulation of epigenetic, transcriptional, and posttranscriptional events. Long non-coding RNA expression patterns in various malignant tumors differ from those of benign tumors and normal tissue, and such alterations may promote or suppress tumorigenesis and cancer progression. The expression profiles of lncRNAs are abnormal in gynecological cancers, such as ovarian cancer, cervical cancer, and endometrial cancer, suggesting an important role for lncRNAs in tumorigenesis/progression of these cancers. Here, we summarized the research progress on identifying the biological functions of lncRNAs in tumorigenesis, progression, and metastasis in gynecological cancers. We provide references for exploring the clinical applications of lncRNAs as early diagnostic biomarkers or ideal therapeutic targets in gynecological cancers.

Myeloid-derived suppressor cells (MDSCs) are present in most cancer patients. Due to their significant role in blocking immune responses, MDSCs are strategic obstacles to immunotherapy that require activation of the host's cell-mediated and innate immune responses. Following a brief description of the immunosuppressive MDSCs, the authors review the discovered mechanisms of amino acid metabolism that MDSCs use to suppress the activation of T cells. Given the heterogeneity of MDSCs and the variety of suppressive mechanisms employed by MDSCs, it is essential to understand which group of these cells and mechanisms are dominant.