ALC1蛋白在食管鳞癌中的表达及其对细胞增殖侵袭迁移的影响

目的:探讨ALC1(amplified in liver cancer 1)在食管鳞癌组织中的表达及与临床病理特征及总生存率关系,检测过表达ALC1基因对食管癌细胞恶性生物学行为的影响。方法:采用免疫组织化学方法检测245例食管鳞癌组织及癌旁组织中ALC1蛋白的表达,并探讨其与食管鳞癌患者性别、年龄、分化程度、浸润深度、TNM分期、远处淋巴结转移关系及总生存率关系;采用MTT法、克隆形成实验、Transwell实验及细胞划痕实验等观察高表达ALC1基因在食管癌细胞中的增殖、侵袭及迁移作用。结果:ALC1蛋白在食管癌组织中的阳性表达率明显高于癌旁组织(41.6%vs.21.2%,P<0.05);ALC1的高表达与肿瘤的浸润深度、TNM分期和淋巴结转移明显相关(P<0.05)。ALC1高表达的食管鳞癌患者总生存率低。ALC1基因能够促进KYSE30食管癌细胞过度增殖、侵袭和迁移。结论:ALC1表达升高可能与食管鳞癌的发生、发展相关,导致总生存率下降,高表达的ALC1基因增强KYSE30食管癌细胞的增殖、侵袭及迁移能力,检测ALC1可能为食管癌预后判断提供依据。

KIF2C:a novel link between Wnt/β-catenin and mTORCI signaling in the pathogenesis of hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is the most common primary liver malignancy and is the fourth-leading cause of cancer-related deaths worldwide.HCC is refractory to many standard cancer treatments and the prognosis is often poor,highlighting a pressing need to identify biomarkers of aggressiveness and potential targets for future treatments.Kinesin family member 2C(KIF2C)is reported to be highly expressed in several human tumors.Nevertheless,the molecular mechanisms underlying the role of KIF2C in tumor development and progression have not been investigated.In this study,we found that KIF2C expression was significantly upregulated in HCC,and that KIF2C up-regulation was associated with a poor prognosis.Utilizing both gain and loss of function assays,we showed that KIF2C promoted HCC cell proliferation,migration,invasion,and metastasis both in vitro and in vivo.Mechanistically,we identified TBC1D7 as a binding partner of KIF2C,and this interaction disrupts the formation of the TSC complex,resulting in the enhancement of mammalian target of rapamycin complexl(mTORCI)signal transduction.Additionally,we found that KIF2C is a direct target of the Wnt/β-catenin pathway,and acts as a key factor in mediating the crosstalk between Wnt/β-catenin and mTORCI signaling.Thus,the results of our study establish a link between Wnt/β-catenin and mTORCI signaling,which highlights the potential of KIF2C as a therapeutic target for the treatment of HCC.

Cancer cell reprogramming:a promising therapy converting malignancy to benignity

In the past decade, remarkable progress has been made in reprogramming terminally differentiated somatic cells and cancer cells into induced pluripotent cells and cancer cells with benign phenotypes. Recent studies have explored various approaches to induce reprogramming from one cell type to another, including lineage-specific transcription factors-, combinatorial small molecules-, microRNAs- and embryonic microenvironment-derived exosome-mediated reprogramming. These reprogramming approaches have been proven to be technically feasible and versatile to enable re-activation of sequestered epigenetic regions, thus driving fate decisions of differentiated cells. One of the significant utilities of cancer cell reprogramming is the therapeutic potential of retrieving normal cell functions from various malignancies. However, there are several major obstacles to overcome in cancer cell reprogramming before clinical translation, including characterization of reprogramming mechanisms, improvement of reprogramming efficiency and safety, and development of delivery methods. Recently, several insights in reprogramming mecha-nism have been proposed, and determining progress has been achieved to promote reprogramming efficiency and feasibility, allowing it to emerge as a promising therapy against cancer in the near future. This review aims to discuss recent applications in cancer cell reprogramming, with a focus on the clinical significance and limitations of different reprogramming approaches, while summarizing vital roles played by transcription factors, small molecules, microR-NAs and exosomes during the reprogramming process.

The predictive value of chromosome 8p deletion for metastasis of hepatocellular carcinoma:a summary of works in 10 years

Hepatocellular carcinoma(HCC)represents an extremely poor prognostic cancer,which is mainly due to the high frequency of metastasis/recurrence after surgical operation.Exploring the molecular mechanisms involved in HCC metastasis could be helpful in the pre-diction and early diagnosis of HCC recurrence and could also provide new therapeutic targets for HCC metastasis.In the recent decade,we analyzed the genomic aberrations of the clinical specimens,as well as the metastatic models and cell lines of human HCC to identify the genetic mar-kers related to HCC metastasis and to verify their clinical values in the prediction and control of metastasis of HCC.Using the comparative genomic hybridization(CGH)technique,we compared the differences of chromosomal aberrations between primary HCC tumors and their matched metastatic lesions,and found that chromosome 8p deletions might contribute to HCC metastasis.This novel finding was further confirmed by comparison between nude mice models of HCC with different meta-static potentials.By the more sensitive genome-wide microsatellite analysis,8p deletion was defined to 8p23.3 and 8p11.2,which are two likely regions harboring meta-stasis-related genes of HCC.Using‘8p-specific’microar-rays,two novel metastatic suppressors(HTPAP and MRSA)were identified,and were proven to suppress in vitro invasion and in vivo metastasis of HCC.Clinical studies indicate that 8p deletion detected in HCC or cir-culating plasma DNA of patients is a useful predictor for metastatic recurrence and prognosis,even for patients with early stage HCC.These novel findings are regarded as important advances in the study of the molecular mechanisms of HCC metastasis,which provide not only a holistic view on the molecular cytogenetic bases of HCC metastasis,but also candidate regions for further study to identify metastatic suppressor genes.