Optimizing metastatic-cascade-dependent Rac1 targeting in breast cancer: Guidance using optical window intravital FRET imaging.

A Floerchinger; Murphy KJ; Latham SL; Warren SC; McCulloch AT; Lee YK; J Stoehr; P Mélénec; Guaman CS; Metcalf XL; V Lee; A Zaratzian; Silva A Da; M Tayao; S Rolo; M Phimmachanh; G Sultani; L McDonald; Mason SM; N Ferrari; Ooms LM; Johnsson AE; Spence HJ; Olson MF; Machesky LM; Sansom OJ; Morton JP; Mitchell CA; Samuel MS; Croucher DR; Welch HCE; K Blyth; Caldon CE; D Herrmann; Anderson KI; P Timpson; M Nobis

doi:10.1016/j.celrep.2021.109689

Optimizing metastatic-cascade-dependent Rac1 targeting in breast cancer: Guidance using optical window intravital FRET imaging.

A Floerchinger, Murphy KJ, Latham SL, Warren SC, McCulloch AT, Lee YK, J Stoehr, P Mélénec, Guaman CS, Metcalf XL, V Lee, A Zaratzian, Silva A Da, M Tayao, S Rolo, M Phimmachanh, G Sultani, L McDonald, Mason SM, N FerrariOoms LM, Johnsson AE, Spence HJ, Olson MF, Machesky LM, Sansom OJ, Morton JP, Mitchell CA, Samuel MS, Croucher DR, Welch HCE, K Blyth, Caldon CE, D Herrmann, Anderson KI, P Timpson, M Nobis

Research output: Contribution to journal › Article › peer-review

Abstract

Assessing drug response within live native tissue provides increased fidelity with regards to optimizing efficacy while minimizing off-target effects. Here, using longitudinal intravital imaging of a Rac1-Förster resonance energy transfer (FRET) biosensor mouse coupled with in vivo photoswitching to track intratumoral movement, we help guide treatment scheduling in a live breast cancer setting to impair metastatic progression. We uncover altered Rac1 activity at the center versus invasive border of tumors and demonstrate enhanced Rac1 activity of cells in close proximity to live tumor vasculature using optical window imaging. We further reveal that Rac1 inhibition can enhance tumor cell vulnerability to fluid-flow-induced shear stress and therefore improves overall anti-metastatic response to therapy during transit to secondary sites such as the lung. Collectively, this study demonstrates the utility of single-cell intravital imaging in vivo to demonstrate that Rac1 inhibition can reduce tumor progression and metastases in an autochthonous setting to improve overall survival.

Original language	English
Journal	Cell Reports
DOIs	https://doi.org/10.1016/j.celrep.2021.109689
Publication status	Published - 1 Sept 2021

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10.1016/j.celrep.2021.109689

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Floerchinger, A., KJ, M., SL, L., SC, W., AT, M., YK, L., Stoehr, J., Mélénec, P., CS, G., XL, M., Lee, V., Zaratzian, A., Da, S. A., Tayao, M., Rolo, S., Phimmachanh, M., Sultani, G., McDonald, L., SM, M., ... Nobis, M. (2021). Optimizing metastatic-cascade-dependent Rac1 targeting in breast cancer: Guidance using optical window intravital FRET imaging. Cell Reports. https://doi.org/10.1016/j.celrep.2021.109689

@article{29a6090b79cb47c5a8301401132a3226,

title = "Optimizing metastatic-cascade-dependent Rac1 targeting in breast cancer: Guidance using optical window intravital FRET imaging.",

abstract = "Assessing drug response within live native tissue provides increased fidelity with regards to optimizing efficacy while minimizing off-target effects. Here, using longitudinal intravital imaging of a Rac1-F{\"o}rster resonance energy transfer (FRET) biosensor mouse coupled with in vivo photoswitching to track intratumoral movement, we help guide treatment scheduling in a live breast cancer setting to impair metastatic progression. We uncover altered Rac1 activity at the center versus invasive border of tumors and demonstrate enhanced Rac1 activity of cells in close proximity to live tumor vasculature using optical window imaging. We further reveal that Rac1 inhibition can enhance tumor cell vulnerability to fluid-flow-induced shear stress and therefore improves overall anti-metastatic response to therapy during transit to secondary sites such as the lung. Collectively, this study demonstrates the utility of single-cell intravital imaging in vivo to demonstrate that Rac1 inhibition can reduce tumor progression and metastases in an autochthonous setting to improve overall survival.",

author = "A Floerchinger and Murphy KJ and Latham SL and Warren SC and McCulloch AT and Lee YK and J Stoehr and P M{\'e}l{\'e}nec and Guaman CS and Metcalf XL and V Lee and A Zaratzian and Da, \{Silva A\} and M Tayao and S Rolo and M Phimmachanh and G Sultani and L McDonald and Mason SM and N Ferrari and Ooms LM and Johnsson AE and Spence HJ and Olson MF and Machesky LM and Sansom OJ and Morton JP and Mitchell CA and Samuel MS and Croucher DR and Welch HCE and K Blyth and Caldon CE and D Herrmann and Anderson KI and P Timpson and M Nobis",

year = "2021",

month = sep,

day = "1",

doi = "10.1016/j.celrep.2021.109689",

language = "English",

journal = "Cell Reports",

issn = "2211-1247",

publisher = "Cell Press",

}

Floerchinger, A, KJ, M, SL, L, SC, W, AT, M, YK, L, Stoehr, J, Mélénec, P, CS, G, XL, M, Lee, V, Zaratzian, A, Da, SA, Tayao, M, Rolo, S, Phimmachanh, M, Sultani, G, McDonald, L, SM, M, Ferrari, N, LM, O, AE, J, HJ, S, MF, O, LM, M, OJ, S, JP, M, CA, M, MS, S, DR, C, HCE, W, Blyth, K, CE, C, Herrmann, D, KI, A, Timpson, P & Nobis, M 2021, 'Optimizing metastatic-cascade-dependent Rac1 targeting in breast cancer: Guidance using optical window intravital FRET imaging.', Cell Reports. https://doi.org/10.1016/j.celrep.2021.109689

TY - JOUR

T1 - Optimizing metastatic-cascade-dependent Rac1 targeting in breast cancer: Guidance using optical window intravital FRET imaging.

AU - Floerchinger, A

AU - KJ, Murphy

AU - SL, Latham

AU - SC, Warren

AU - AT, McCulloch

AU - YK, Lee

AU - Stoehr, J

AU - Mélénec, P

AU - CS, Guaman

AU - XL, Metcalf

AU - Lee, V

AU - Zaratzian, A

AU - Da, Silva A

AU - Tayao, M

AU - Rolo, S

AU - Phimmachanh, M

AU - Sultani, G

AU - McDonald, L

AU - SM, Mason

AU - Ferrari, N

AU - LM, Ooms

AU - AE, Johnsson

AU - HJ, Spence

AU - MF, Olson

AU - LM, Machesky

AU - OJ, Sansom

AU - JP, Morton

AU - CA, Mitchell

AU - MS, Samuel

AU - DR, Croucher

AU - HCE, Welch

AU - Blyth, K

AU - CE, Caldon

AU - Herrmann, D

AU - KI, Anderson

AU - Timpson, P

AU - Nobis, M

PY - 2021/9/1

Y1 - 2021/9/1

N2 - Assessing drug response within live native tissue provides increased fidelity with regards to optimizing efficacy while minimizing off-target effects. Here, using longitudinal intravital imaging of a Rac1-Förster resonance energy transfer (FRET) biosensor mouse coupled with in vivo photoswitching to track intratumoral movement, we help guide treatment scheduling in a live breast cancer setting to impair metastatic progression. We uncover altered Rac1 activity at the center versus invasive border of tumors and demonstrate enhanced Rac1 activity of cells in close proximity to live tumor vasculature using optical window imaging. We further reveal that Rac1 inhibition can enhance tumor cell vulnerability to fluid-flow-induced shear stress and therefore improves overall anti-metastatic response to therapy during transit to secondary sites such as the lung. Collectively, this study demonstrates the utility of single-cell intravital imaging in vivo to demonstrate that Rac1 inhibition can reduce tumor progression and metastases in an autochthonous setting to improve overall survival.

AB - Assessing drug response within live native tissue provides increased fidelity with regards to optimizing efficacy while minimizing off-target effects. Here, using longitudinal intravital imaging of a Rac1-Förster resonance energy transfer (FRET) biosensor mouse coupled with in vivo photoswitching to track intratumoral movement, we help guide treatment scheduling in a live breast cancer setting to impair metastatic progression. We uncover altered Rac1 activity at the center versus invasive border of tumors and demonstrate enhanced Rac1 activity of cells in close proximity to live tumor vasculature using optical window imaging. We further reveal that Rac1 inhibition can enhance tumor cell vulnerability to fluid-flow-induced shear stress and therefore improves overall anti-metastatic response to therapy during transit to secondary sites such as the lung. Collectively, this study demonstrates the utility of single-cell intravital imaging in vivo to demonstrate that Rac1 inhibition can reduce tumor progression and metastases in an autochthonous setting to improve overall survival.

UR - https://doi.org/10.1016/j.celrep.2021.109689

U2 - 10.1016/j.celrep.2021.109689

DO - 10.1016/j.celrep.2021.109689

M3 - Article

C2 - 34525350

SN - 2211-1247

JO - Cell Reports

JF - Cell Reports

ER -

Optimizing metastatic-cascade-dependent Rac1 targeting in breast cancer: Guidance using optical window intravital FRET imaging.

Abstract

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