Background: NCAPD3 is one of the three non-SMC subunits of condensin II complex, which plays an important role in the chromosome condensation and segregation during mitosis. Notably, elevated levels of NCAPD3 are found in many somatic cancers. However, the clinical role, biological functions of NCAPD3 in cancers especially in colorectal cancer (CRC) and the underlying molecular mechanisms remain poorly elucidated. Methods: Clinical CRC and adjacent normal tissues were used to confirm the expression of NCAPD3. The association of NCAPD3 expression with clinicopathological characteristics and patient outcomes were analyzed by using online database. In vivo subcutaneous tumor xenograft model, NCAPD3 gene knockout following azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced tumor mouse model, Co-IP, western blot, qRT-PCR, IHC, ChIP assays and cell functional assays were used to investigate the biological functions of NCAPD3 in CRC and the underlying molecular mechanisms. Results: NCAPD3 was overexpressed in CRC tissues and positively correlated with poor prognosis of CRC patients. NCAPD3 knockout suppressed CRC development in AOM/DSS induced and xenograft mice models. Moreover, we found that NCAPD3 promoted aerobic glycolysis in CRC. Mechanistically, NCAPD3 up-regulated the level of c-Myc and interacted with c-Myc to recruit more c-Myc to the gene promoter of its downstream glycolytic regulators GLUT1, HK2, ENO1, PKM2 and LDHA, and finally enhanced cellular aerobic glycolysis. Also, NCAPD3 increased the level of E2F1 and interacted with E2F1 to recruit more E2F1 to the promoter regions of PDK1 and PDK3 genes, which resulted in the inhibition of PDH activity and TCA cycle. Conclusions: Our data demonstrated that NCAPD3 promoted glucose metabolism reprogramming and enhanced Warburg effect in colorectal tumorigenesis and CRC progression. These findings reveal a novel mechanism underlying NCAPD3 mediated CRC cell growth and provide new targets for CRC treatment.

CXCL13 is androgen-responsive and involved in androgen induced prostate cancer cell migration and invasion CXCL13 is androgen-responsive and involved in androgen induced prostate cancer cell migration and invasion

Traditional Chinese medicine (TCM) has a combined therapeutic result in cancer treatment by integrating holistic and local therapeutical effects, by which TCM can enhance the curative effect and reduce the side effect. In this study, we analyzed the effect of CFF‐1 (alcohol extract from an anticancer compound Chinese medicine) on prostate cancer (PCa) cell lines and studied in detail the mechanism of cell death induced by CFF‐1 in vitro and in vivo. From our data, we found for the first time that CFF‐1 obviously arrested cell cycle in G1 phase, decreased cell viability and then increased nuclear rupture in a dose‐dependent manner and finally resulted in apoptosis in prostate cancer cells. In molecular level, our data showed that CFF‐1 induced inhibition of EGFR auto‐phosphorylation and inactivation of EGFR. Disruption of EGFR activity in turn suppressed downstream PI3K/AKT and Raf/Erk signal pathways, resulted in the decrease of p‐FOXO1 (Ser256) and regulated the expression of apoptosis‐related and cycle‐related genes. Moreover, CFF‐1 markedly induced cell autophagy through inhibiting PI3K/AKT/mTOR pathway and then up‐regulating Beclin‐1 and LC‐3II and down‐regulating phosphorylation of p70S6K. In vivo, CFF‐1‐treated group exhibited a significant decrease in tumor volume compared with the negative control group in subcutaneous xenograft tumor in nude mice via inhibiting EGFR‐related signal pathways. Thus, bio‐functions of Chinese medicine CFF‐1 in inducing PCa cell growth inhibition, autophagy, and apoptosis suggested that CFF‐1 had the clinical potential to treat patients with prostate cancer.