A mechano-signalling network linking microtubules, myosin IIA filaments and integrin-based adhesions

Rafiq, Nisha Bte Mohd; Nishimura, Yukako; Plotnikov, Sergey V.; Thiagarajan, Visalatchi; Zhang, Zhen; Shi, Shidong; Natarajan, Meenubharathi; Viasnoff, Virgile; Kanchanawong, Pakorn; Jones, Gareth E.; Bershadsky, Alexander D.

doi:10.1038/s41563-019-0371-y

Cited by 139 publications

(165 citation statements)

References 55 publications

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“…The increased sensitivity of MDA-MB-435S cells to both MT poisons upon integrin αV or KANK2 knockdown points to altered MT dynamics in these cells. Consistently, recent data in other cell models have shown that KANK proteins mediate crosstalk between actin and MT cytoskeletons at FAs (Bouchet et al, 2016;Sun et al, 2016;Chen et al, 2018;Rafiq et al, 2019).…”

Section: Discussionsupporting

confidence: 83%

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

Paradžik

Humphries

Stojanović

et al. 2020

Front. Cell Dev. Biol.

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Section: Discussionsupporting

confidence: 83%

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

Paradžik

Humphries

Stojanović

et al. 2020

Front. Cell Dev. Biol.

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“…KANK1 has an essential role in cytoskeleton maintenance via regulating the rate of cytoskeleton proteins production and controlling actin polymerisation [4]. KANK1 plays an important role in the down-regulation of the Rho-associated kinase (ROCK) pathway [5], which is recognised to be involved in various cellular functions such as proliferation, adhesion, cell differentiations and apoptosis [6]. This allow KANK1 to integrate alongside with β-catenin aiming to regulate its distribution in the nucleus and concentrate its transcription, therefore, affecting the development of cancer [7].…”

Section: Introductionmentioning

confidence: 99%

Prognostic significance of KN motif and ankyrin repeat domains 1 (KANK1) in invasive breast cancer

Kariri

Joseph

Kurozumi

et al. 2019

Breast Cancer Res Treat

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Background KN motif and ankyrin repeat domains 1 (KANK1) plays an important role in cytoskeleton maintenance and contributes to the regulation of cell proliferation, adhesion and apoptosis. KANK1 is involved in progression of a variety of solid tumours; however, its role in invasive breast cancer (BC) remains unknown. This study aims to evaluate the clinicopathological and prognostic value of KANK1 expression in operable BC. Methods KANK1 expression was assessed at the transcriptomic level using multiple BC cohorts; the Molecular Taxonomy of BC International Consortium cohort (METABRIC; n = 1980), The Cancer Genome Atlas BC cohort (TCGA; n = 949) and the publicly available BC transcriptomic data hosted by BC Gene-Expression Miner (bc-GenExMiner v4.0) and Kaplan-Meier plotter?. The Nottingham BC cohort (n = 1500) prepared as tissue microarrays was used to assess KANK1 protein expression using immunohistochemistry (IHC). The association between clinicopathological variables and patient outcome was investigated. Results In the METABRIC cohort, high expression of KANK1 mRNA was associated with characteristics of good prognosis including lower grade, absence of lymphovascular invasion and HER2 negativity (all; p < 0.001) and with better outcome [p = 0.006, Hazards ratio, (HR) 0.70, 95% CI 0.54-0.91]. High KANK1 protein expression was correlated with smaller tumour size and HER2 negativity, and better outcome in terms of longer breast cancer-specific survival [p = 0.013, HR 0.7, 95% CI 0.536-0.893] and time to distant metastasis [p = 0.033, HR 0.65, 95% CI 0.51-0.819]. Conclusion These results supported that upregulation of KANK1 works as a tumour suppressor gene in BC and is associated with improved patients' outcomes.

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“…In addition, the four KANK proteins, KANK1-KANK4, have been described as 'seeds' that initiate the formation of a cortical platform assembly for the stabilisation of microtubules (Bouchet et al, 2016;Sun et al, 2016). KANK1 and KANK2 localise around FAs and podosomes (Rafiq et al, 2019). KANK1 links the CMSC to FAs through its direct interaction with both talin and liprin-β1 (Bouchet et al, 2016;Sun et al, 2016).…”

Section: Recruitment Of Cortical Partners Near Fasmentioning

confidence: 99%

“…How the GEF-H1 interaction with microtubules is regulated is still a matter of debate. Uncoupling microtubules from FAs, by depleting KANKs, releases GEF-H1 from microtubules (Rafiq et al, 2019), which indicates that anchoring microtubules at FAs inhibits GEF-H1 and may act as a negative-feedback loop to prevent excessive acto-myosin-mediated forces at FAs. Signalling cascades involving the serine threonine kinase Par1b/MARK2, as well as p21-activated-kinase 4 (PAK4), phosphorylate GEF-H1, which promotes its release from microtubules (Callow et al, 2005;Yoshimura and Miki, 2011).…”

Section: Meddling With the Fa-actin Duomentioning

confidence: 99%

Microtubules at focal adhesions – a double-edged sword

Seetharaman

Etienne-Manneville

2019

Journal of Cell Science

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Cell adhesion to the extracellular matrix is essential for cellular processes, such as migration and invasion. In response to cues from the microenvironment, integrin-mediated adhesions alter cellular behaviour through cytoskeletal rearrangements. The tight association of the actin cytoskeleton with adhesive structures has been extensively studied, whereas the microtubule network in this context has gathered far less attention. In recent years, however, microtubules have emerged as key regulators of cell adhesion and migration through their participation in adhesion turnover and cellular signalling. In this Review, we focus on the interactions between microtubules and integrin-mediated adhesions, in particular, focal adhesions and podosomes. Starting with the association of microtubules with these adhesive structures, we describe the classical role of microtubules in vesicular trafficking, which is involved in the turnover of cell adhesions, before discussing how microtubules can also influence the actin-focal adhesion interplay through RhoGTPase signalling, thereby orchestrating a very crucial crosstalk between the cytoskeletal networks and adhesions.

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A mechano-signalling network linking microtubules, myosin IIA filaments and integrin-based adhesions

Abstract: A mechano-signalling network linking microtubules, myosin IIA filaments and integrin-based adhesions.

Cited by 139 publications

References 55 publications

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

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

Prognostic significance of KN motif and ankyrin repeat domains 1 (KANK1) in invasive breast cancer

Microtubules at focal adhesions – a double-edged sword

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