KANK2 Links αVβ5 Focal Adhesions to Microtubules and Regulates Sensitivity to Microtubule Poisons and Cell Migration

Paradžik, Mladen; Humphries, Jonathan D.; Stojanović, Nikolina; Nestić, Davor; Majhen, Dragomira; Dekanić, Ana; Samaržija, Ivana; Sedda, Delphine; Weber, Igor; Ambriović-Ristov, Andreja

doi:10.3389/fcell.2020.00125

Cited by 28 publications

(81 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Yet, how exactly the removal of KANK2 reduces migration velocity remains unclear. We never observed any significant effects on FAs, neither in size nor number which is in line with the observations of Sun et al and Paradzik et al who also did not see any effects on FA size or number upon KANK2 depletion (Paradžik et al, 2020;Sun et al, 2016). Further, the removal of KANK2 from SUM159PT cells did not affect the formation and clustering of the CMSC components such as liprin-β1 or CLASP2 around FAs.…”

Section: Discussionsupporting

confidence: 92%

“…Sun et al showed that depletion of mouse KANK2 in mouse fibroblasts led to accelerated cell migration (Sun et al, 2016); whereas Gee et al have described that loss of mouse KANK2 in cultured mouse podocytes leads to reduced cell migration (Gee et al, 2015). More recently, it was shown that knockdown of KANK2 in the melanoma cell line MDA-MB-435S negatively affected cell migration (Paradžik et al, 2020). In our wound healing experiments, we saw that removal of both KANK1 and KANK2 did not affect migration of HeLa cells.…”

Section: Discussionmentioning

confidence: 47%

See 1 more Smart Citation

Linking cell-matrix adhesions and microtubules: the role of KANK proteins

Ammon¹

View full text Add to dashboard Cite

Structure of the KANK family proteins Characteristic for the KANK family proteins is their structure with three distinct domains (Figure 3). At the N-terminus, all KANK proteins possess a highly conserved so-called KANK N-terminal (KN) domain, an α-helix with a leucine-aspartic acid (LD) motif, which mediates binding of KANK1 and 2 to talin (Bouchet et al., 2016; Sun et al., 2016; Yu et al., 2019). For KANK3 and 4 binding to talin has not been shown yet; however, due to the high conservation of the KN domains among the KANK family it is expected that KANK3 and 4 can bind to talin as well. Moreover, all KANKs possess at least one coiled coil domain located in the central region of the protein. In total there exist four different conserved coiled coil domains (CC1-4) among the KANK family, the composition of the different coiled coils differs between the four KANK paralogs (Zhu et al., 2008). Van der Vaart et al. have found that KANK coiled coil domain 1 (CC1) mediates binding to liprin-β1, a member of the family of LAR transmembrane tyrosine phosphatase-interacting proteins, at the cell cortex in the vicinity of adhesion complexes (van der Vaart et al., 2013). At their C-terminus all KANK family members contain an ankyrin repeat domain which was shown to bind to the kinesin-4 motor protein KIF21A (Kakinuma and Kiyama, 2009; van der Vaart et al., 2013). Interestingly, the majority of studies reported that the KANK ankyrin repeat domain consists of five repeats of the ankyrin motif (Ankr1-5) (

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 47%

Linking cell-matrix adhesions and microtubules: the role of KANK proteins

Ammon¹

View full text Add to dashboard Cite

show abstract

“…Namely, the expression of integrin subunits β1, β3 and α4 is increased while expression of α2, α5, α8, β4 and β6 is decreased as compared to normal tissue ( Figure 2 ). However, increased expression of integrins α5β1 and αvβ3 results in a poor melanoma prognosis, increased cell invasion, and metastasis [ 61 , 62 ], while data obtained in vitro in different melanoma cell lines showed that integrin αvβ5 is involved in the higly aggressive phenotype of cells expressing neuropilin 1 [ 63 ], and is involved in sensitivity to microtubule poison paclitaxel and increased in vitro migration and invasion [ 64 , 65 ].…”

Section: The Integrin Repertoire Is Changed or ”Switched” In Cancementioning

confidence: 99%

“…Integrin signalling confers either primary or adaptive resistance of cancer cells to chemotherapy and radiotherapy [ 7 , 18 , 124 ] which are still the treatments of choice for many solid tumors. Therefore, different integrins remain interesting targets for the sensitization of tumor cells, or even cancer stem cells to chemotherapy and radiotherapy, but also inhibit metastasis, as it has been shown for breast carcinoma [ 64 , 125 , 126 ], head and neck squamous cell carcinoma [ 127 ], glioblastoma [ 128 , 129 ], melanoma [ 65 , 130 ], prostate cancer [ 131 ], ovarian cancer [ 132 ], lung cancer [ 133 ] and many others. Recent data have shown that integrin signalling confers resistance to targeted agents like vemurafenib [ 134 ] or lapatinib and trastuzumab [ 135 ].…”

Section: Is Integrin Crosstalk One Of the Reasons For Integrin Tarmentioning

confidence: 99%

Integrin Crosstalk Contributes to the Complexity of Signalling and Unpredictable Cancer Cell Fates

Samaržija

Dekanić

Humphries

et al. 2020

Cancers

Self Cite

View full text Add to dashboard Cite

Integrins are heterodimeric cell surface receptors composed of α and β subunits that control adhesion, proliferation and gene expression. The integrin heterodimer binding to ligand reorganises the cytoskeletal networks and triggers multiple signalling pathways that can cause changes in cell cycle, proliferation, differentiation, survival and motility. In addition, integrins have been identified as targets for many different diseases, including cancer. Integrin crosstalk is a mechanism by which a change in the expression of a certain integrin subunit or the activation of an integrin heterodimer may interfere with the expression and/or activation of other integrin subunit(s) in the very same cell. Here, we review the evidence for integrin crosstalk in a range of cellular systems, with a particular emphasis on cancer. We describe the molecular mechanisms of integrin crosstalk, the effects of cell fate determination, and the contribution of crosstalk to therapeutic outcomes. Our intention is to raise awareness of integrin crosstalk events such that the contribution of the phenomenon can be taken into account when researching the biological or pathophysiological roles of integrins.

show abstract

“…There are four potential axes that link integrins to actin, all implicated in different stages of NA formation, namely (i) integrin-linked kinase-particularly interesting new cysteine-histidine rich protein-1-kindlin, (ii) focal adhesion kinase (FAK)-paxillin, (iii) talin-vinculin and (iv) α-actinin-zyxin-vasodilator-stimulated phosphoprotein (Winograd-Katz et al, 2014;Horton et al, 2015Horton et al, , 2016Humphries et al, 2019). Interestingly, some adaptors, such as talin, also coordinate the microtubule cytoskeleton at adhesion sites through the interaction with KANK proteins (KN motif and ankyrin repeat-containing proteins) (Bouchet et al, 2016;Sun et al, 2016;Chen et al, 2018;Paradžik et al, 2020), which was shown to stimulate FA turnover (Stehbens and Wittmann, 2012). How early this connection is established and the implication to NAs is still unresolved.…”

Section: The Key Molecular Players In Nascent Adhesionsmentioning

confidence: 99%

Recent Advances and Prospects in the Research of Nascent Adhesions

et al. 2020

Self Cite

View full text Add to dashboard Cite

Nascent adhesions are submicron transient structures promoting the early adhesion of cells to the extracellular matrix. Nascent adhesions typically consist of several tens of integrins, and serve as platforms for the recruitment and activation of proteins to build mature focal adhesions. They are also associated with early stage signaling and the mechanoresponse. Despite their crucial role in sampling the local extracellular matrix, very little is known about the mechanism of their formation. Consequently, there is a strong scientific activity focused on elucidating the physical and biochemical foundation of their development and function. Precisely the results of this effort will be summarized in this article.

show abstract

KANK2 Links αVβ5 Focal Adhesions to Microtubules and Regulates Sensitivity to Microtubule Poisons and Cell Migration

Cited by 28 publications

References 54 publications

Linking cell-matrix adhesions and microtubules: the role of KANK proteins

Linking cell-matrix adhesions and microtubules: the role of KANK proteins

Integrin Crosstalk Contributes to the Complexity of Signalling and Unpredictable Cancer Cell Fates

Recent Advances and Prospects in the Research of Nascent Adhesions

Contact Info

Product

Resources

About