TY - JOUR

T1 - ACK1 is dispensable for development, skin tumor formation, and breast cancer cell proliferation

AU - Brandao, Rafael

AU - Kwa, Mei Qi

AU - Yarden, Yossi

AU - Brakebusch, Cord

N1 - This article is protected by copyright. All rights reserved.

PY - 2021

Y1 - 2021

N2 - ACK1, a widely expressed non-receptor tyrosine kinase, is often amplified in cancer and has been shown to interact with Cdc42, EGFR and several other cancer relevant molecules, suggesting a possible role for ACK1 in development and tumor formation. To directly address this scenario, we generated mice lacking a functional ACK1 gene (ACK1 ko) using CRISPR genome editing. ACK1 ko mice developed normally, displayed no obvious defect in tissue maintenance and were fertile. Primary ACK1-null keratinocytes showed normal phosphorylation of EGFR, but a tendency towards reduced activation of Akt and Erk. DMBA/TPA induced skin tumor formation did not reveal significant differences between ACK1 ko and control mice. Deletion of the ACK1 gene in the breast cancer cells lines MDA-MB-231, 67NR, MCF7, 4T1 and T47D caused no differences in growth. Furthermore, EGF-induced phosphorylation kinetics of Erk, Akt and p130Cas were not detectably altered in T47D cells by the loss of ACK1. Finally, loss of ACK1 in MDA-MB-231 and T47D breast cancer cells had a very limited or no effect on directed cell migration. These data do not support a major role for ACK1 in Cdc42 and EGFR signaling, development, or in tumor formation.

AB - ACK1, a widely expressed non-receptor tyrosine kinase, is often amplified in cancer and has been shown to interact with Cdc42, EGFR and several other cancer relevant molecules, suggesting a possible role for ACK1 in development and tumor formation. To directly address this scenario, we generated mice lacking a functional ACK1 gene (ACK1 ko) using CRISPR genome editing. ACK1 ko mice developed normally, displayed no obvious defect in tissue maintenance and were fertile. Primary ACK1-null keratinocytes showed normal phosphorylation of EGFR, but a tendency towards reduced activation of Akt and Erk. DMBA/TPA induced skin tumor formation did not reveal significant differences between ACK1 ko and control mice. Deletion of the ACK1 gene in the breast cancer cells lines MDA-MB-231, 67NR, MCF7, 4T1 and T47D caused no differences in growth. Furthermore, EGF-induced phosphorylation kinetics of Erk, Akt and p130Cas were not detectably altered in T47D cells by the loss of ACK1. Finally, loss of ACK1 in MDA-MB-231 and T47D breast cancer cells had a very limited or no effect on directed cell migration. These data do not support a major role for ACK1 in Cdc42 and EGFR signaling, development, or in tumor formation.

U2 - 10.1002/2211-5463.13149

DO - 10.1002/2211-5463.13149

M3 - Journal article

C2 - 33730447

VL - 11

SP - 1579

EP - 1592

JO - FEBS Open Bio

JF - FEBS Open Bio

SN - 2211-5463

IS - 6

ER -