TABLE 2.

Functional and mechanistic roles of annexin dysregulation in cancer biology.

Roles of annexin dysregulation in cancer biology
Annexin	Tissue expression	Structural singularities	Biological function	Signaling pathways
ANXA1	Ubiquitous		Cell Proliferation; Apoptosis; Differentiation; Cell Migration; Invasion; Immunomodulation; Inflammation; Membrane remodeling; Membrane trafficking; Phagocytosis; Cell adhesion; Cell-cell communication; Autophagy (Alldridge and Bryant, 2003; Solito et al., 2003; Petrella et al., 2005; Lim and Pervaiz, 2007; D’Acquisto et al., 2008; Yi and Schnitzer, 2009; Li et al., 2011; Dalli et al., 2012; Yang et al., 2013; Cooray et al., 2013; Gastardelo et al., 2014; Bist et al., 2015; Zhu et al., 2018; Raulf et al., 2018)	GC mediator; EGFR, HGFR, PDGFR and PKC substrate; Regulation of NFκB, ERK-MAPK, Rho-GTPases, EGFR/STAT3, PI3K/AKT and TRAIL pathways; Participate in BAD dephosphorylation; FPR ligand; PLA2 inhibition; BECN1 inhibition; M2 macrophage differentiation (Davidson et al., 1991; Raynal and Pollard, 1994; Alldridge and Bryant, 2003; Solito et al., 2003; Petrella et al., 2005; Lim and Pervaiz, 2007; Zhang et al., 2010; Li et al., 2011; Cooray et al., 2013; Gastardelo et al., 2014; Bist et al., 2015; Gobbetti and Cooray, 2016; Zhu et al., 2018; Araújo et al., 2021)
ANXA2	Ubiquitous	Key phosphorylation residues Ser11, Ser25 and Tyr23 (Liu et al., 2003a)	Cell Proliferation; Differentiation; Cell Migration; Invasion; Membrane remodeling; Membrane trafficking; Immunomodulation; Angiogenesis (Creutz, 1992; Harder and Gerke, 1993; Merrifield et al., 2001; Zobiack et al., 2003; Benaud et al., 2004; Morel and Gruenberg, 2007; de Graauw et al., 2008; Bao et al., 2009; Shetty et al., 2012; Chao et al., 2015; Rocha et al., 2018; Mahdi et al., 2020; Mao et al., 2021)	Regulation of DOCK3/β-Cat/WAVE2, TGF-β, AKT, Twist/Snail and JNK/cJun pathways; Src/ANXA2/STAT3 and EphA2/YES1/ANXA2 axis (Rescher et al., 2008; Kanagasabai et al., 2010; Zheng et al., 2011; Wang et al., 2012; Chen et al., 2015; Cui et al., 2016; Feng et al., 2017; Rocha et al., 2018; Mao et al., 2021)
ANXA3	Ubiquitous	Two relevant tryptophan residues (W5 and W190) (Sopkova et al., 2009)	Cell Proliferation; Apoptosis; Cell Migration; Angiogenesis; Inflammation; Membrane remodeling; Membrane trafficking (Gerke and Moss, 2002; Park et al., 2005; Chong et al., 2010; Faugaret et al., 2011; Meng et al., 2019; Zhang et al., 2021b)	Regulation of ERK, JNK, PI3K/AKT and EGFR pathway; PLA2 inhibition (Coméra et al., 1990; Ruan et al., 2010; Tong et al., 2015; Xu et al., 2019a; Wan et al., 2020)
ANXA4	Ubiquitous		Cell Migration; Invasion; Membrane remodeling (Kaetzel et al., 2001; Jiang et al., 2018; Xu et al., 2019b; Wang et al., 2020; Florentsen et al., 2021)	Regulation of PI3K/AKT/eNOS pathway; Adenylyl cyclase 5 inhibition (Heinick et al., 2015, 2020; Xu et al., 2019b)
ANXA5	Ubiquitous		Cell Proliferation; Cell Migration; Invasion; Cell adhesion; Membrane remodeling (Bouter et al., 2015; Ding et al., 2017; Li et al., 2018; Sun et al., 2018; Bouvet et al., 2020)	Regulation of ERK pathway (Wang et al., 2021)
ANXA6	Ubiquitous	8 annexin repeats forming 2 cores in C-terminal (Qi et al., 2015)	Cell proliferation; Cell Migration; Invasion; Cell adhesion; Membrane remodeling; Membrane trafficking, Autophagy; Cholesterol homeostasis (Potez et al., 2011; Swaggart et al., 2014; Qi et al., 2015; Boye et al., 2017; Grewal et al., 2017)	Regulation of EGFR/Ras/MAPK, FAK/PI3K and YAP pathway; Regulation of calcium entry (Pons et al., 2001; Grewal et al., 2005, 2017; Monastyrskaya et al., 2009; Muga et al., 2009; Cornely et al., 2011; Koese et al., 2013; Wang et al., 2013; Qi et al., 2015)
ANXA7	Ubiquitous	Long hydrophobic N-terminal (Grewal et al., 2016)	Cell proliferation; Calcium homeostasis; Membrane trafficking; Aggregation of chromaffin granules (Gerke and Moss, 2002; Grewal et al., 2016)	Regulation of COX-dependent PGE2 production; Regulation of EGFR pathway; GTPase function (Grewal et al., 2016)
ANXA8	Placenta and skin		Cell Adhesion; Angiogenesis; Membrane remodeling; Membrane trafficking; Endosomes biology (Goebeler et al., 2006, 2008; Poeter et al., 2014; Heitzig et al., 2017)	Participation in VEGFR signaling (Heitzig et al., 2017)
ANXA9	Ubiquitous	Unable to bind calcium (Morgan et al., 1999a)	Cell proliferation; Cell Migration; Invasion; Epidermis biology (Boczonadi and Määttä, 2012; Yu et al., 2018; Zhou et al., 2021)	Regulation of TGF-β pathway (Zhou et al., 2021)
ANXA10	Stomach	Unable to bind calcium (Morgan et al., 1999b)	Transcription regulator (Quiskamp et al., 2014)	Regulation of Akt and ERK/MAPK pathway (Kodaira et al., 2019)
ANXA11	Ubiquitous	Long hidrofobic N-terminal (Gerke and Moss, 2002)	Cell proliferation; Apoptosis; Membrane remodeling; Membrane trafficking; Sex differentiation (Wang et al., 2014)	Regulation of Cell cycle progression (Wang et al., 2014)
ANXA13	Small intestine	Myristoylated at N-terminal (Gerke and Moss, 2002)	Membrane trafficking; Lipid-raft dynamics (Lafont et al., 1998; Plant et al., 2000)