Role of AMPK and Akt in triple negative breast cancer lung colonization
| Autor: | Heidi L. Weiss, B. Mark Evers, Jeremy Johnson, Zeta Chow, Piotr G. Rychahou, Eun Y. Lee |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Cancer Research IHC Immunohistochemistry Lung Neoplasms AKT1 AKT2 Apoptosis Triple Negative Breast Neoplasms Mice SCID AMP-Activated Protein Kinases Mice 0302 clinical medicine Circulating tumor cell Akt Protein kinase B Mice Inbred NOD PS Pencillin-streptomycin RPMI Roswell Park Memorial Institute Triple negative breast cancer RNA Small Interfering Triple-negative breast cancer AMPKα Neoplastic Cells Circulating lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ER+ Estrogen receptor-positive WB Western blot 030220 oncology & carcinogenesis GFP Green fluorescent protein siRNA Small interfering RNA Female RNA Interference Signal transduction TNBC Triple negative breast cancer Heterocyclic Compounds 3-Ring Signal Transduction Original article PBS Phosphate buffered saline Biology lcsh:RC254-282 NSG NOD-scid IL2Rgammanull 03 medical and health sciences Cell Line Tumor Animals Humans Neoplasm Invasiveness Pyrroles Protein kinase B Akt AMPK Organ metastasis AMPK AMP-activated protein kinase 030104 developmental biology Pyrimidines Cancer cell Cancer research FBS Fetal bovine serum Energy Metabolism Proto-Oncogene Proteins c-akt |
| Zdroj: | Neoplasia: An International Journal for Oncology Research, Vol 23, Iss 4, Pp 429-438 (2021) Neoplasia (New York, N.Y.) |
| ISSN: | 1476-5586 |
| Popis: | Triple negative breast cancer (TNBC) is an aggressive disease with a 5-y relative survival rate of 11% after distant metastasis. To survive the metastatic cascade, tumor cells remodel their signaling pathways by regulating energy production and upregulating survival pathways. AMP-activated protein kinase (AMPK) and Akt regulate energy homeostasis and survival, however, the individual or synergistic role of AMPK and Akt isoforms during lung colonization by TNBC cells is unknown. The purpose of this study was to establish whether targeting Akt, AMPKα or both Akt and AMPKα isoforms in circulating cancer cells can suppress TNBC lung colonization. Transient silencing of Akt1 or Akt2 dramatically decreased metastatic colonization of lungs by inducing apoptosis or inhibiting invasion, respectively. Importantly, transient pharmacologic inhibition of Akt activity with MK-2206 or AZD5363 inhibitors did not prevent colonization of lung tissue by TNBC cells. Knockdown of AMPKα1, AMPKα2, or AMPKα1/2 also had no effect on metastatic colonization of lungs. Taken together, these findings demonstrate that transient decrease in AMPK isoforms expression alone or in combination with Akt1 in circulating tumor cells does not synergistically reduce TNBC metastatic lung colonization. Our results also provide evidence that Akt1 and Akt2 expression serve as a bottleneck that can challenge colonization of lungs by TNBC cells. |
| Databáze: | OpenAIRE |
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