Abstract 3042: TPX2 and AURKA promote 20q amplicon driven colorectal adenoma-to-carcinoma progression

Abstract

Background: Gain of a large segment of chromosome 20q is associated with progression of colorectal adenomas into carcinomas, implying that multiple genes on the 20q amplicon drive carcinogenesis. Candidate driver genes are expected to be expressed at mRNA and protein levels that correlate with the 20q amplicon DNA copy number status, while functionally affecting one or several cancer-related processes. Integration of CGH profiles with mRNA profiles of a series of colorectal tumors revealed thirty-two candidate genes whose DNA copy number status correlated with mRNA expression levels. Aim: To functionally analyse the effects of the candidate oncogenes on cancer-related processes by downregulation using siRNA strategies. Results: Downmodulation of TPX2 (20q11.2) and AURKA (20q13.2) mRNA expression in CRC cell lines with 20q gain affected cell viability, anchorage-independent growth, and invasion. Moreover, immunohistochemical evaluation demonstrated a significant correlation between their protein levels and 20q DNA copy number status in a series of colorectal adenomas and carcinomas. Conclusion: These data demonstrate that at least two genes located on distinct regions of chromosome 20q promote colorectal adenoma-to-carcinoma progression and indicate that TPX2, like AURKA, is a promising target for anti-cancer drug development. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3042. doi:10.1158/1538-7445.AM2011-3042

CAPER, a novel regulator of human breast cancer progression

“…25 The expression of CAPER was reported to affect the survival of colorectal cancer cells. 26 Indeed, knockdown of CAPER expression markedly reduced the viability of human colorectal cancer cell lines under both normal culture conditions and upon 5-Fluorodeoxyuridine (5FU)-induced cytotoxicity, suggesting a potential role of CAPER in apoptosis and/or cell senescence. 26 Whether increased apoptosis and/or cell senescence contributed to the reduced tumorigenicity of MCF-7 cells harboring CAPER shRNAs observed herein remains to be determined.…”

“…26 Indeed, knockdown of CAPER expression markedly reduced the viability of human colorectal cancer cell lines under both normal culture conditions and upon 5-Fluorodeoxyuridine (5FU)-induced cytotoxicity, suggesting a potential role of CAPER in apoptosis and/or cell senescence. 26 Whether increased apoptosis and/or cell senescence contributed to the reduced tumorigenicity of MCF-7 cells harboring CAPER shRNAs observed herein remains to be determined. Therefore, future studies will be necessary to address the possible role of CAPER in modulating breast cancer cell apoptosis and senescence.…”

Targeting Protein for Xenopus Kinesin-like Protein 2 (TPX2) Regulates γ-Histone 2AX (γ-H2AX) Levels upon Ionizing Radiation

“…Moreover, TPX2 levels are altered in cancers associated with aberrant cellular responses to DNA damage and genomic instability (12)(13)(14)(15)(16)(17)(18)(19). These observations raise the question as to whether TPX2 is involved in the DNA damage response.…”

“…), and amplification of the TPX2 gene has been suggested to promote the progression of colorectal malignancies (12)(13)(14)(15)(16)(17)(18)(19). Conversely, TPX2 haploinsufficiency, leading to decreased levels of TPX2, significantly increases the propensity for the development of tumors in mice (20).…”

An integrative analysis of colon cancer identifies an essential function for PRPF6 in tumor growth

“…After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http:// creativecommons.org/licenses/by-nc/4.0/. 7 (MET), 8q (MYC), 13 (CDK8 and CDX2), and 20q (AURKA and TPX2) that may play a role in colon cancer cell proliferation (Firestein et al 2008;Dulak et al 2012;Salari et al 2012;Sillars-Hardebol et al 2012;Bardelli et al 2013). However, given the broad nature of chromosomal gain in colonic tumors that frequently span the entire chromosomal arm, we hypothesized that additional genes within these amplicons are necessary for tumor growth.…”