ANXA6: a key molecular player in cancer progression and drug resistance

Abstract

Annexin-A6 (ANXA6), a Ca2+-dependent membrane binding protein, is the largest of all conserved annexin families and highly expressed in the plasma membrane and endosomal compartments. As a multifunctional scaffold protein, ANXA6 can interact with phospholipid membranes and various signaling proteins. These properties enable ANXA6 to participate in signal transduction, cholesterol homeostasis, intracellular/extracellular membrane transport, and repair of membrane domains, etc. Many studies have demonstrated that the expression of ANXA6 is consistently altered during tumor formation and progression. ANXA6 is currently known to mediate different patterns of tumor progression in different cancer types through multiple cancer-type specific mechanisms. ANXA6 is a potentially valuable marker in the diagnosis, progression, and treatment strategy of various cancers. This review mainly summarizes recent findings on the mechanism of tumor formation, development, and drug resistance of ANXA6. The contents reviewed herein may expand researchers’ understanding of ANXA6 and contribute to developing ANXA6-based diagnostic and therapeutic strategies.

Catalytically distinct IDH1 mutants tune phenotype severity in tumor models

“…ANXA6 is a membrane-bound protein that mediates cholesterol transport and homeostasis, and facilitates interactions of the membrane with actin during endocytosis and exocytosis 38 . Notably, it is a tumor suppressor due to its ability two negatively regulate EGFR phosphorylation 39 , and supportive of a lift of a negative regulator, EGFR transcripts were higher in R132Q versus R132H and WT HT1080* xenografts (Supplementary Table 3). Pathways related to lipid catabolism/oxidation were also shown to be downregulated in IDH1 R132Q versus R132H (Fig.…”

The effect of extracellular matrix on the precision medicine utility of pancreatic cancer patient–derived organoids

“…We observed a trend toward upregulation of terms related to cell cycle and translation in hF24, hM1F, and mT69A (Supplemental Figure 11A). Normalized counts of top candidate genes related to proliferation revealed upregulation of a number of genes when hPDOs were cultured in Matrigel, such as ANXA6, elevated levels of which have been described in PDA (25); AQP5, implicated in PDA cell proliferation and biophysical properties of cell membranes (26); and PIK3AP1, a protein capable of activating AKT phosphorylation in gastric cancer (27) (Supplemental Figure 11B). Similarly, in Matrigel, mouse organoids exhibited enriched expression of Spp1, a gene previously identified as a marker of undifferentiated pancreatic progenitors in the ductal niche (28, 29) (Supplemental Figure 11C).…”

The Fundamental Role of Oxime and Oxime Ether Moieties in Improving the Physicochemical and Anticancer Properties of Structurally Diverse Scaffolds

“…Cancer is a generic term used to describe a broad spectrum of diseases characterized by the rapid formation of abnormal cells that grow uncontrollably, extending beyond their usual boundaries and invading adjacent parts of the body while destroying normal tissues [1][2][3]. This condition can affect any part of the body, with the 2020 estimates from the World Health Organization (WHO) indicating that the most common types in terms of new cases were breast cancer (2.26 million cases), lung cancer (2.21 million cases), colon and rectal cancer (1.93 million cases), prostate cancer (1.41 million cases), nonmelanoma skin cancer (1.20 million cases), and stomach cancer (1.09 million cases), with the total number of new cases estimated to 19.3 million [4][5][6][7].…”