The 14-3-3σ Tumor Suppressor Has Multiple Functions in ErbB2-Induced Breast Cancer

Abstract

Ling and colleagues demonstrated that loss of the conditional 14-3-3σ allele results in accelerated HER2/ERBB2-driven mammary tumorigenesis and metastasis. This study underscores the role of 14-3-3σ as a potent tumor suppressor in ERBB2-driven tumor initiation and progression. Cancer Discovery; 2(1); 19–22. ©2012 AACR. Commentary on Ling et al., p. 68.

Estrogen Receptor α/14-3-3 molecular glues as alternative treatment strategy for endocrine resistant breast cancer

“…Multiple studies found a downregulation or degradation of 14-3-3σ expression in some breast cancers, which often related to poor prognosis, and 14-3-3 was therefore considered to be a tumor suppressor. [43][44][45][46][47][48][49][50][51] However, 14-3-3 is still commonly expressed in ERpositive breast cancer (as shown in the Human Protein Atlas) and the expression level of ER is low as compared to 14-3-3σ, thus providing value for exploring molecular glues that can shift the ER14-3-3 binding equilibrium towards the sigma isoform of 14-3-3, thereby enforcing its tumor suppressive role. 52 The most common ER gene mutations linked to endocrine drug resistance are Y537S and D538G.…”

521 Cell Cycle Regulation Changes in Drug-Resistant Cancers

“…SFN was also shown to bind CDKl via its nuclear exporting sequence (NES) and promoted CDKl nuclear exclusion into cytoplasm. The NES is im portant in CDK sequestration since m utant NES o f SFN was unable to sequester CDK out from nucleus is synthesized that leads to incomplete cytokinesis which promotes the development o f pre-cancerous tetraploid lesions (Gardino and Yaffe 2011;Hynes and Smirnova 2012;W ilker et al 2007). In kératinocytes, SFN has been linked to expression o f matrix metalloproteinase 1 (M M P l) via binding to aminopeptidase N (APN), an integral membrane protein th at acts as a cell surface receptor (Ghaffari et al 2010).…”

“…Poor prognosis fo r patients w ith intrahepatic cholangiocarcinoma and prostate cancer was also associated w ith lower SFN expression (Ren et al 2010). In the ErbB2KI transgenic model, loss of either one or both copies o f SFN allele led to accelerated mammary growth (Hynes and Smirnova 2012).…”

“…In breast cancer cell lines, SFN expression is either positively or negatively associated w ith different drug resistant mechanisms (Deng et al 2011;Hynes and Smirnova 2012). Functional proteom ic analysis using two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization tim e-of-flight (MALDI-TOF) mass spectrometry on MCF7 parental and multidrug-resistant MCF7/AdVp3000 revealed that SFN was one o f the protein upregulated in MDR.…”

“…A role played by SFN in drug-resistance has been investigated before (Hynes and Smirnova 2012). In the present study, SFN silencing was introduced to cell lines via siRNA transfection in order to investigate its downregulation in Taxol resistance.…”