Proteomic Differences and Linkages between Chemoresistance and Metastasis of Pancreatic Cancer Using Knowledge-Based Pathway Analysis

Lee, Jingyun; McKinney, Kimberly Q.; Hwang, Sun-Il

doi:10.1016/b978-0-12-408103-1.00010-8

Cited by 2 publications

(1 citation statement)

References 47 publications

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“…TNBC significantly overlaps with the molecular basal-like breast cancer subtype [ 11 ], which can be divided into: basal A, with mixed basal/luminal/epithelial-like features; and basal B, exhibiting mesenchymal-like features and spindle-like morphology [ 12 , 13 ]. The epithelial-like phenotype can, under normal circumstances, switch to the mesenchymal-like phenotype through epithelial–mesenchymal transition (EMT), and in cancer cells, this process has been shown to play a key role in cancer invasion and metastasis [ 14 , 15 , 16 , 17 ]. Recently, we showed that gene copy number variations (CNV) rather than specific mutations are the leading cause of breast cancer spread and lymph node (LN) metastasis [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

Aurora Kinase A and Bcl-xL Inhibition Suppresses Metastasis in Triple-Negative Breast Cancer

Skov

Alves

Ehmsen

et al. 2022

IJMS

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Triple-negative breast cancer (TNBC) is a heterogeneous disease that accounts for 10–15% of all breast cancer cases. Within TNBC, the treatment of basal B is the most challenging due to its highly invasive potential, and thus treatments to suppress metastasis formation in this subgroup are urgently needed. However, the mechanisms underlying the metastatic ability of TNBC remain unclear. In the present study, we investigated the role of Aurora A and Bcl-xL in regulating basal B cell invasion. We found gene amplification and elevated protein expression in the basal B cells, which also showed increased invasiveness in vitro, compared to basal A cells. Chemical inhibition of Aurora A with alisertib and siRNA-mediated knockdown of BCL2L1 decreased the number of invading cells compared to non-treated cells in basal B cell lines. The analysis of the correlation between AURKA and BCL2L1 expression in TNBC and patient survival revealed significantly decreased relapse-free survival (n = 534, p = 0.012) and distant metastasis-free survival (n = 424, p = 0.017) in patients with primary tumors exhibiting a high combined expression of AURKA and BCL2L1. Together, our findings suggest that high levels of Aurora A and Bcl-xL promote metastasis, and inhibition of these proteins may suppress metastasis and improve patient survival in basal B TNBC.

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