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Review
. 2022 Aug 14;11(16):2521.
doi: 10.3390/cells11162521.

Cell Cycle Regulation by Integrin-Mediated Adhesion

Siamak A Kamranvar  1 , Bhavna Rani  1 , Staffan Johansson  1
Affiliations
Review

Cell Cycle Regulation by Integrin-Mediated Adhesion

Siamak A Kamranvar et al. Cells. .

Abstract

Cell cycle and cell adhesion are two interdependent cellular processes regulating each other, reciprocally, in every cell cycle phase. The cell adhesion to the extracellular matrix (ECM) via integrin receptors triggers signaling pathways required for the cell cycle progression; the passage from the G1 to S phase and the completion of cytokinesis are the best-understood events. Growing evidence, however, suggests more adhesion-dependent regulatory aspects of the cell cycle, particularly during G2 to M transition and early mitosis. Conversely, the cell cycle machinery regulates cell adhesion in manners recently shown driven mainly by cyclin-dependent kinase 1 (CDK1). This review summarizes the recent findings regarding the role of integrin-mediated cell adhesion and its downstream signaling components in regulating the cell cycle, emphasizing the cell cycle progression through the G2 and early M phases. Further investigations are required to raise our knowledge about the molecular mechanisms of crosstalk between cell adhesion and the cell cycle in detail.

Keywords: G2 phase; adhesion; cell cycle; integrin; mitosis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
A schematic picture showing some of the main components of CAs, the interaction of cell cycle kinase CDK1 with talin, and the central adhesion-dependent events regulating the G1 to S transition. Paxillin both links kindlin to the GTP-Rap1-activated talin and recruits FAK to the complex. Integrin α-units are shown in blue and the β-units are in white. The red lines represent the extracellular matrix.
Figure 2
Figure 2
The schematic top view picture indicates that the number and size of CA area is shrinking in the G2 phase mainly due to the inactivation of cyclin A2/CDK1 in the G2 phase while RAs are maintained.
Figure 3
Figure 3
The schematic side view picture indicates cell rounding and the remnants of cell adhesions. The activation of cyclin B/CDK1 and the downstream degradation of kindlin and activation of the RhoA pathway, together with the inactivation of RAP1-GTPase are described as the main mechanisms for cell rounding in mitosis.
Figure 4
Figure 4
The components of CAs are involved in the cell cycle progression through the G2 phase and early mitosis where cyclin B/CDK1 and PLK1 play critical roles.
Figure 5
Figure 5
The schematic picture demonstrates the spindle orientation and some of the microtubule- and retraction fiber-associated proteins.
Figure 6
Figure 6
A proposed model for the role of integrin-mediated adhesion signaling via FAK and Src in cytokinesis abscission. Adhesion is indicated to delay the degradation of PLK1 and, thereby, prevent premature recruitment of Cep55 to the midbody; the details of this mechanism are incompletely known. In the absence of adhesion, Alix and TSG101 do not bind to Cep55 and the abscission process cannot proceed further.
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Grants and funding

The Swedish Cancer Foundation funded this research, grant number 19 0531 Pj.

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