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Fig. 1 | Journal of Hematology & Oncology

Fig. 1

From: Integrins regulate stemness in solid tumor: an emerging therapeutic target

Fig. 1

Integrin structure and integrin signalosome. a Schematic domain structure of a generic integrin. The α subunit contains 8 β-propeller domain repeats, a thigh domain, two calf domains (Calf-1 and Calf-2) and an α-tail domain. Notably, for 9 out of 18 α subunits, there is an I-domain inserted between β propeller domains 2 and 3. The β subunit typically comprises a plexin-semaphorin-integrin (PSI) domain, an I-like domain followed by a β-sandwich hybrid domain, four cysteine-rich integrin epidermal growth factor-like (I-EGF) repeats and a β-tail domain. b Bidirectional integrin signalosome. Integrins exist in different conformational states that determine the receptor affinity for ECM components and other ligands: from a bent-closed (inactive) to an extended closed (active with low affinity) and finally to an extended open conformation (active with high affinity). When binding to ECM proteins, integrins are activated and clustered, and are capable of eliciting downstream signaling and controlling cellular responses to environmental cues (outside-in signaling). Integrins also response to an “inside-out signaling”, whereby Talin binding to the β integrin tail triggers conformational switch to an extended open state and further recruit integrin activating proteins such as Kindlins to activate integrin. The most well-studied hub pathway activated by integrins is focal adhesion kinase (FAK), with subsequent recruitment and activation of the Src family kinase (SFK), which ultimately affects cell behavior via crosstalk with many other signaling effectors. See text for details

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