Anchorage-independent cell growth signature identifies tumors with metastatic potential

Abstract

The oncogenic phenotype is complex, resulting from the accumulation of multiple somatic mutations that lead to the deregulation of growth regulatory and cell fate controlling activities and pathways. The ability to dissect this complexity, so as to reveal discrete aspects of the biology underlying the oncogenic phenotype, is critical to understanding the various mechanisms of disease as well as to reveal opportunities for novel therapeutic strategies. Previous work has characterized the process of anchorageindependent growth of cancer cells in vitro as a key aspect of the tumor phenotype, particularly with respect to metastatic potential. Nevertheless, it remains a major challenge to translate these cell biology findings into the context of human tumors. We previously used DNA microarray assays to develop expression signatures, which have the capacity to identify subtle distinctions in biological states and can be used to connect in vitro and in vivo states. Here we describe the development of a signature of anchorage-independent growth, show that the signature exhibits characteristics of deregulated mitochondrial function and then demonstrate that the signature identifies human tumors with the potential for metastasis.

An integrated computational and experimental study uncovers FUT 9 as a metabolic driver of colorectal cancer

“…These experiments revealed that the knockdown of FUT9 in both cell lines significantly increases their expansion compared to matching non‐targeting sh RNA controls (Fig 3A). In agreement, FUT9 silencing also enhanced anchorage‐independent growth in soft agar (Mori et al , 2009) (Fig 3B). Moreover, the loss of FUT9 augmented the ability of cancer cells to form colonies in monolayers, when cells were seeded at very low densities (Fig 3D).…”

KR-33028, a potent inhibitor of the Na+/H+ exchanger NHE1, suppresses metastatic potential of triple-negative breast cancer cells

“…In vitro anchorage-independent colony growth embedded in soft agar is an important assessment of tumorigenicity [21], and is considered to be predictive of the ability of tumor cells to form new metastases in vivo [25], so inhibition of this growth by KR-33028, even in the non-tumorigenic Hs578T cells, is noteworthy. However, despite the efficacy of KR-33028 in limiting colony growth in TNBC cells, the drug did not affect cell proliferation at non-cytotoxic concentrations.…”

The stem cell transcription factor ZFP57 induces IGF2 expression to promote anchorage-independent growth in cancer cells

“…Anchorage-independent growth is therefore a major characteristic of transformed cells, and in fact shows a good correlation with tumor malignancy. 38,39 In addition to cancer cells, Zfp57 is involved in ES cell anchorage-independent growth, suggesting that ZFP57-mediated anchorage-independent growth is not restricted to cancer cells. Furthermore, ZFP57…”