Together, these data demonstrate an unanticipated requirement for non-canonical EGFR signaling in cancer cell extrusion, which might act in part by promoting E-cadherin endocytosis.
First-pass extracted concept
non-canonical EGFR signaling
Candidate: concept label1 source documents5 linked claims
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Linked Claims
EGFR activity in Ras(Q61L)-expressing cells is required for efficient extrusion, because erlotinib treatment or EGFR deletion suppresses extrusion.
Quoted textsource-backed
Unexpectedly, however, extrusion was suppressed by erlotinib, an inhibitor of epidermal growth factor receptor (EGFR), and by deletion of EGFR. EGFR expression was not required in surrounding wild-type cells but was needed by the Ras(Q61L) cells for extrusion
Deletion of SOS1 and SOS2 does not block extrusion, supporting that the EGFR contribution to extrusion is not mediated through canonical SOS-dependent Ras activation.
Quoted textsource-backed
yet deletion of the Ras guanine-nucleotide-exchange factors SOS1 and SOS2 (SOS1/2) did not block extrusion.
Ras expression triggers E-cadherin internalization, and EGFR inhibition partially blocks this internalization.
Quoted textsource-backed
Notably, expression of Ras triggered internalization of E-cadherin (CDH1), which was partially blocked by EGFR inhibition.
The EGFR requirement for Ras(Q61L)-driven extrusion is non-canonical because EGFR inhibition or deletion does not reduce Ras(Q61L)-GTP levels or ERK phosphorylation.
Quoted textsource-backed
However, EGFR inhibition or deletion had no impact on Ras(Q61L)-GTP levels or ERK phosphorylation.
Constitutively active MEK is sufficient to drive extrusion, and EGFR inhibition still reduces extrusion in these cells.
Quoted textsource-backed
Moreover, expression of a constitutively active MEK instead of Ras was sufficient to drive extrusion, and EGFR inhibition in these cells reduced extrusion.