Targeting Spindle-Associated Protein HAUS6 Prevents Cell Growth of Colorectal Cancer Cells by Activating the p53/p21 Pathway

Abstract

Background: HAUS6 participates in microtubule-dependent microtubule amplification, but its role in malignancies including colorectal cancer (CRC) has not been explored. We therefore assessed the potential oncogenic activities of HAUS6 in CRC.Methods: We investigated HAUS6 expression and its prognostic value in CRC by microarray, analysis of public datasets, quantitative reverse transcription - polymerase chain reaction (qRT-PCR) and immunohistochemistry. Biological functions of HAUS6 were investigated using loss-of-function and gain-of-function assays in vivo and/or in vitro. Effectors downstream of HAUS6 were identified using cDNA microarray, bioinformatics analysis, qRT-PCR and western-blotting in CRC cells. The putative mechanism by which HAUS6 knockdown elevated p53 and p21 expression were assessed by rescue experiment. The combination effects of HAUS6 knockdown and 5-fluorouracil (5-FU) treatment in cultured CRC cells were further evaluated. Results: HAUS6 mRNA and protein expression is higher in CRC tissues, and high HAUS6 expression is correlated with shorter overall survival in CRC patients. HAUS6 knockdown in CRC cell lines suppressed cell growth in vitro and in vivo by inhibiting cell viability, survival and arresting cell cycle progression at G0/G1, while HAUS6 over-expression increased cell viability. We showed that these effects are dependent on activation of the p53/p21 signalling pathway by reducing p53 and p21 degradation. Moreover, HAUS6 knockdown enhanced the effects of 5-FU treatment in CRC cells by increasing activation of the p53/p21 pathway.Conclusions: Our study highlights a potential oncogenic role for HAUS6 in CRC. Targeting HAUS6 may be a promising novel prognostic marker and chemotherapeutic target for treating CRC patients.

Correlation between Genomic Variants and Worldwide Epidemiology of Prostate Cancer

“…HAUS6 is part of the group of augmin complex subunits, which play an important role in the recruitment and amplification of microtubule molecules during cell division [ 26 ]. Our analysis demonstrated a significant correlation of rs1048169 in this gene with incidence and mortality, which were higher in the African population.…”