Overexpression of Dock180 and Elmo1 in melanoma is associated with cell survival and migration

Abstract

Melanoma is one of the most aggressive and metastatic skin cancers, of these metastatic melanoma is a lethal disease with invasive behavior. Although overexpression of Dock180 and Elmo1 has been identified in various cancers, including glioma, ovarian cancer, hepatocellular carcinoma, and breast cancer, the expression and functions of them in melanoma remain unknown. Therefore, the purpose of this study is to confirm the expression of Dock180 and Elmo1, their underlying mechanisms, and roles in melanoma. Both immunohistochemical staining and Western blotting were used to confirm expression of Dock180 and Elmo1 in human melanoma and normal skin. To identify roles of Dock180 and Elmo1 in cell survival, apoptosis and migration, downregulation of Dock180 or Elmo1 in melanoma cells treated with siRNA was performed in Cell viability assay, Phase contrast images, DAPI staining, Cell cycle analysis, Apoptosis assay, Wound healing assay, Colony formation assay, and Western blotting. We identified overexpression of Dock180 and Elmo1 in human melanoma compared to normal skin ex vivo. Inhibition of Dock180 or Elmo1 following siRNA treatment in melanoma cells reduced cell viability and increased apoptosis as supported by increased proportion of cells with Annexin V-PE(+) staining and sub-G0/G1 peak in cell cycle analysis. Moreover, inhibition of Dock180 or Elmo1 regulated apoptosis-related proteins, showing downregulaton of Bcl-2, caspase-3, and PARP and upregulation of Bax, PUMA, cleaved caspase3, and cleaved PARP. Furthermore, knockdown of Dock180 and Elmo1 in melanoma cells reduced cell migration and changed cellular signaling pathways including ERK and AKT. Vemurafenib treatment decreased cell viability in a concentration-dependent manner, while transfection with Dock180- or Elmo1-specific siRNA in melanoma cells significantly reduced cell viability compared to non-transfected cells. Collectively, these findings suggest that both Dock180 and Elmo1 may be associated with cancer progression such as cell survival and migration in melanoma, and can be potential targets for treatment of melanoma.

Impact of Renal Function on Short-Term Outcome After Reperfusion Therapy in Patients With Ischemic Stroke

“…gov; Unique identifier: NCT02964052) 2 and the Yonsei Stroke Cohort (YSC; Clinicaltrials.gov NCT03510312). 7 Details regarding this registry and cohort have been published previously and are summarized in the Supplemental Methods. We included 1026 patients who were registered retrospectively between January 2012 and December 2015, and 333 who were registered prospectively between November 2016 and December 2017 from the SECRET study, and 1522 patients who received reperfusion therapy and were registered prospectively in the YSC database between January 2000 and September 2019.…”

Coagulation Factor Expression and Composition of Arterial Thrombi in Cancer-Associated Stroke

“…This retrospective analysis used data from a prospective hospital-based stroke registry (Yonsei Stroke Cohort; https:// www.clinicaltrials.gov; NCT03510312) and enrolled consecutive patients with acute ischemic stroke within 7 days after symptom onset. 15 Patients were routinely evaluated with brain imaging studies (magnetic resonance imaging or computed tomography), angiographic studies (magnetic resonance angiography, computed tomography angiography, or conventional angiography), cardiac evaluations (echocardiography, continuous electrocardiography monitoring at the stroke unit or 24-hour Holter monitoring, and cardiac computed tomography), and standard blood tests. Blood samples for complete blood counts, prothrombin time, and activated partial thromboplastin time were collected upon the patient's arrival at the emergency department or before EVT in the case of inhospital stroke.…”