Targeting HCC Therapy: On or Off ToPiX?

摘要: Primary liver cancer, the fifth most frequently diagnosed cancer worldwide, is second common cause of mortality [1]. Among primary cancers, hepatocellular carcinoma (HCC) accounts for 70–85 % total burden worldwide [2]. Epidemiological evidence suggests that several environmental factors are involved in development HCC, including infection with hepatitis B (HBV) and C (HCV) viruses. Globally, HBV frequent underlying an estimated 300 million persons chronic worldwide. Chronic HCV also a major risk factor HCC. There preliminary indicating host genetic may contribute to progression [3]. Assessment aberrations revealed mutations well-known tumor suppressor gene p53 amplification human chromosome 20q region up 30 HCC cases [4]. Targeting protein Xenopus kinesin-like 2 (TPX2) microtubule-associated encoded by located on 20q11. Several studies report multiple types overexpress TPX2; TPX2 expression tissues correlates tumor– node–metastasis stage (TNM), number, differentiation. Liu et al. [5] described as novel prognostic marker predicting overall 5-year disease-free survival patients. In vitro, knockdown significantly inhibited cell proliferation viability Hep3B HepG2 cells. Moreover, noticeably slowed down growth nude mouse xenograft model prominently suppressed invasion migration [6]. localizes nucleus during S-phase G2 at mitotic spindle poles mitosis [7] emphasizing its likely involvement division. Yet, full connection remains largely undetermined, only few have investigated this protein. issue Digestive Diseases Sciences, Lian [8] effects cycle, apoptosis, epithelial-to-mesenchymal transition (EMT) fundamental tumorigenesis. They reported mRNA levels were elevated tumors 70 paired versus adjacent non-tumor tissues, localized nuclei. Using siRNA-mediated loss TPX2, authors G2/M cycle arrest, reduced proliferation, induction apoptosis three lines, alteration key regulators cyclin A1, B1, D1, E1, p21, regulator D1. Genomic lesions usually repaired before onset DNA replication If damage not repairable, programed death termed occurs limit cells defective DNA. The induces arrest or partly through Bax, transcriptional target p53. Bax was increased TPX2-siRNA HCC-derived drives damaged promoting apoptosis-related enzymes cleaved caspase-3 caspase-8 upregulated following loss, further supporting anti-apoptosis function (Fig. 1). & Claudia D. Andl claudia.andl@vanderbilt.edu