Annexin-A1 – A Blessing or a Curse in Cancer?

ANXA1, an originally anti-inflammatory mediator is implicated in cancer, although its functions in cancer growth and metastasis are unclear and conflicting. ANXA1 expression is lost in some cancers; mostly squamous cell carcinomas and those located in the upper region of the body. Its expression is enhanced in other cancers, predominantly in the gut. In hairy cell leukemia and cholangiocarcinoma it is a clinical biomarker. Expression of ANXA1 may be dependent on stage or type in other cancers (e.g., breast or thyroid). ANXA1 acts as a double-edged sword as it is generally antiproliferative, protecting cells against DNA damage, while it promotes metastasis. ANXA1 can be post-translationally modified, through phosphorylation and sumoylation, and can inhibit miRNAs in a negative feedback loop. The use of ANXA1 as a therapeutic or prognostic marker for cancer must be carefully timed, depending on cancer type, grade, and stage. Annexin-A1 (ANXA1), a potent endogenous immunomodulatory protein has been implicated in multiple functions essential in cancer, including cell proliferation, apoptosis, chemosensitivity, metastasis, and invasion. ANXA1 expression is varied depending on tumor type, and there are contradictory reports on its role in the regulation of proliferation and tumor growth. Here, we summarize the differing reports on cell proliferation and metastasis and attempt to discuss the reasons behind these different effects. ANXA1 plays a role as a homeostatic protein that regulates essential transcription factors and miRNAs. A more coherent understanding of ANXA1 in cancer could present a more biologically meaningful and clinically relevant strategy. Annexin-A1 (ANXA1), a potent endogenous immunomodulatory protein has been implicated in multiple functions essential in cancer, including cell proliferation, apoptosis, chemosensitivity, metastasis, and invasion. ANXA1 expression is varied depending on tumor type, and there are contradictory reports on its role in the regulation of proliferation and tumor growth. Here, we summarize the differing reports on cell proliferation and metastasis and attempt to discuss the reasons behind these different effects. ANXA1 plays a role as a homeostatic protein that regulates essential transcription factors and miRNAs. A more coherent understanding of ANXA1 in cancer could present a more biologically meaningful and clinically relevant strategy. the polarized epithelial cell can change to a mesenchymal cell phenotype via multiple biological processes. This transition causes a series of biochemical changes to the cells, enhancing the migratory capacity, invasiveness, elevated resistance to apoptosis, and increased ECM components such as N-cadherin and fibronectin. Once the EMT process is complete, the underlying basement membrane that interacted with the epithelial cell before the transition degrades, and the newly formed mesenchymal cell migrates away. a noncellular component of extracellular molecules secreted by support cells which provides structural and biochemical support to the surrounding cells. Due to the evolution of independent cell lineages, the composition of ECM varies between multicellular structures. The ECM is composed of proteoglycans and fibrous proteins. MMPs (also known as matrixins) are calcium-dependent zinc-containing endopeptidases. MMPs are the main group of enzymes responsible for collagen degradation as well as the degradation of the ECM. lymph node status shows whether or not the lymph nodes in the underarm area (axillary nodes) contain cancer: lymph node-negative means the lymph nodes do not contain cancer, while lymph node-positive means the lymph nodes contain cancer. Prognosis is poorer when cancer has spread to the lymph nodes (lymph node-positive). The number of positive nodes guides treatment and helps predict the chances for long-term survival. commonly used to generate more relevant murine models of cancer, where the tumor cells are injected into the native organ from which they originated. a post-translational modification process which occurs via SUMO proteins. Like ubiquitination, SUMOylation is directed by an enzymatic cascade. SUMOylation involves a cascade of three enzymes: the E1-activating complex SAE1/SAE2, the E2-conjugating enzyme UBC9, and one of the several E3 ligases (such as PIAS superfamily or RANBP2). However, in contrast to ubiquitin, SUMO is not used to tag proteins for degradation but affects a protein’s structure and subcellular localization. multifunctional polypeptide that plays an essential role in tumor proliferation, differentiation, angiogenesis, and other functions. The TGF-β pathway includes the canonical SMAD pathway signaling and DAXX pathway, which induces apoptosis, or programmed cell death, in human lymphocytes and hepatocytes. Like a double-edged sword, TGF-β acts as a tumor suppressor in the early stage of tumor progression in normal epithelial cells. In advanced cancers, TGF-β enhances cell growth, invasion, and metastasis. refers to the type of breast cancer that does not express the genes for estrogen receptor (ER−), progesterone receptor (PR−), and HER2−. This type of breast cancer is not supported by the hormones estrogen and progesterone, which makes it more difficult to treat. Generally, triple-negative cancers often require combination chemotherapy and target therapies.