ABSTRACT
When breast cancer progresses to a metastatic stage, survival rates decline rapidly and it is considered incurable. Thus, deciphering the critical mechanisms of metastasis is of vital importance to develop new treatment options. We hypothesize that studying the proteins that are newly synthesized during the metastatic processes of migration and invasion will greatly enhance our understanding of breast cancer progression. We conducted a mass spectrometry screen following bioorthogonal noncanonical amino acid tagging to elucidate changes in the nascent proteome that occur during epidermal growth factor stimulation in migrating and invading cells. Annexin A2 was identified in this screen and subsequent examination of breast cancer cell lines revealed that Annexin A2 is specifically upregulated in estrogen receptor negative (ER-) cell lines. Furthermore, siRNA knockdown showed that Annexin A2 expression promotes the proliferation, wound healing and directional migration of breast cancer cells. In patients, Annexin A2 expression is increased in ER- breast cancer subtypes. Additionally, high Annexin A2 expression confers a higher probability of distant metastasis specifically for ER- patients. This work establishes a pivotal role of Annexin A2 in breast cancer progression and identifies Annexin A2 as a potential therapeutic target for the more aggressive and harder to treat ER- subtype.
Subject(s)
Annexin A2/metabolism , Breast Neoplasms/metabolism , Annexin A2/genetics , Blotting, Western , Breast Neoplasms/genetics , Carrier Proteins/genetics , Carrier Proteins/metabolism , Cell Line, Tumor , Cell Movement/genetics , Cell Movement/physiology , Cell Proliferation/genetics , Cell Proliferation/physiology , Electrophoresis, Polyacrylamide Gel , Female , Humans , Immunoprecipitation , MCF-7 Cells , Mass Spectrometry , RNA, Small Interfering/genetics , RNA, Small Interfering/metabolism , Receptors, Estrogen/genetics , Receptors, Estrogen/metabolismABSTRACT
Bleeding per rectum is a relatively common acute surgical presentation. Common causes include diverticular disease, colitis, haemorrhoids, polyps, etc. An 83-year-old man with a history of recurrent rectosigmoid diverticulitis and bilateral internal iliac artery aneurysms for 2 years presented with rectal bleeding. He was suspected to have a diverticular bleed based on history and examination. A CT scan revealed a large haematoma adjacent to the right isolated internal iliac artery aneurysm (IIIAA) almost indistinguishable from the adjacent rectosigmoid, consistent with a ruptured IIIAA and an ileorectal fistula. The fistula was of a primary vascular enteric type and was accentuated by the inflammation arising from the diverticulitis. Hence, presence of more common or apparently obvious causes should not deter clinicians from thoroughly investigating the case. Rare causes should be kept in mind while dealing with common acute presentations, especially in elderly patients with multiple comorbidities.
