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Review
. 2023 May 2;14(1):53.
doi: 10.1007/s12672-023-00662-x.

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

Jinlong Cao #  1   2 , Shun Wan #  1   2 , Siyu Chen #  1   2 , Li Yang  3   4
Affiliations
Review

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

Jinlong Cao et al. Discov Oncol. .

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.

Keywords: ANXA6; Drug resistance; Membrane repair; Metabolic reprogramming; Migration.

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Conflict of interest statement

The authors declare no competing financial interests.

Figures

Fig. 1
Fig. 1
ANXA6 may affect the downstream pathway by inhibiting EGFR phosphorylation. ANXA6, as a scaffold protein of Protein kinase Cα (PKCα), PKCα phosphorylates EGFR at threonine 654 to inhibit EGFR tyrosine phosphorylation and related activation of downstream effectors. Moreover, ANXA6 forms protein complexes with H-Ras, p120GAP, and EGFR that inhibit p120GAP/Ras assembly and inhibit Ras signaling
Fig. 2
Fig. 2
Role of ANXA6 in late endosomal (LE) and lysosome (Lys) cholesterol transport and caveolae formation. WT (low-level ANXA6) cell is shown in the left panel. The blue arrow shows the pathway of Caveolin-1 (Cav-1) from the endoplasmic reticulum (ER) to the cytomembrane. Red arrows indicate cholesterol uptake, transport from LEs to Golgi and efflux. In cells with high ANXA6 levels (right panel), cholesterol buildup in LEs is accompanied by ANXA6 translocation to LE/ multivesicular bodies (MVBs), where ANXA6 interferes with the Niemann-Pick C1 (NPC1) protein to inhibit cholesterol output to the Golgi. Excessive accumulation of LE/Lys cholesterol interferes with the transport of Cav-1 to the cell surface dependent on cytoplasmic phospholipase A2α (cPLA2α). And ultimately leads to the reduction of Cav-1 and cholesterol in the plasma membrane and subsequent caveolae formation and signaling
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References

    1. Moss SE, Morgan RO. The annexins. Genome Biol. 2004;5(4):219. doi: 10.1186/gb-2004-5-4-219. - DOI - PMC - PubMed
    1. Creutz CE, Pazoles CJ, Pollard HB. Identification and purification of an adrenal medullary protein (synexin) that causes calcium-dependent aggregation of isolated chromaffin granules. J Biol Chem. 1978;253(8):2858–66. doi: 10.1016/S0021-9258(17)40901-X. - DOI - PubMed
    1. Huang KS, et al. Two human 35 kd inhibitors of phospholipase A2 are related to substrates of pp60v-src and of the epidermal growth factor receptor/kinase. Cell. 1986;46(2):191–9. doi: 10.1016/0092-8674(86)90736-1. - DOI - PubMed
    1. Iglesias JM, et al. Comparative genetics and evolution of annexin A13 as the founder gene of vertebrate annexins. Mol Biol Evol. 2002;19(5):608–18. doi: 10.1093/oxfordjournals.molbev.a004120. - DOI - PubMed
    1. Boye TL, et al. Annexins induce curvature on free-edge membranes displaying distinct morphologies. Sci Rep. 2018;8(1):10309. doi: 10.1038/s41598-018-28481-z. - DOI - PMC - PubMed

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