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Review
. 2022 Mar 23:10:833663.
doi: 10.3389/fcell.2022.833663. eCollection 2022.

Endogenous and Exogenous Regulatory Signaling in the Secretory Pathway: Role of Golgi Signaling Molecules in Cancer

Simona Del Giudice  1 , Valentina De Luca  1 , Seyedehnegar Parizadeh  1 , Domenico Russo  1 , Alberto Luini  1 , Rosaria Di Martino  1
Affiliations
Review

Endogenous and Exogenous Regulatory Signaling in the Secretory Pathway: Role of Golgi Signaling Molecules in Cancer

Simona Del Giudice et al. Front Cell Dev Biol. .

Abstract

The biosynthetic transport route that constitutes the secretory pathway plays a fundamental role in the cell, providing to the synthesis and transport of around one third of human proteins and most lipids. Signaling molecules within autoregulatory circuits on the intracellular membranes of the secretory pathway regulate these processes, especially at the level of the Golgi complex. Indeed, cancer cells can hijack several of these signaling molecules, and therefore also the underlying regulated processes, to bolster their growth or gain more aggressive phenotypes. Here, we review the most important autoregulatory circuits acting on the Golgi, emphasizing the role of specific signaling molecules in cancer. In fact, we propose to draw awareness to highlight the Golgi-localized regulatory systems as potential targets in cancer therapy.

Keywords: Golgi; cancer; control system; protein transport; secretion; secretory pathway; signaling.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor declared a past collaboration with one of the authors AL.

Figures

FIGURE 1
FIGURE 1
The secretory pathway is a signaling platform. The secretory pathway hosts several signaling machineries, whose function as autoregulatory systems has been characterized in detail. The ER localized AREX complex (1) and LTK-dependent system (2) are involved in regulating ER export of different proteins. Once proteins leave the ER, also ER resident chaperones reach the cis-Golgi, where they bind and activate the KDELR. Indeed, the KDELR activation stimulates both the Gs-PKA signaling (3) to regulate retrograde traffic and the Gq-SRC pathway (4) to promote the anterograde transport through the Golgi. Finally, proteins reach the TGN to be sorted and reach the final destination either inside or outside the cell. Specifically, basolateral proteins stimulate the GPRC5A receptor to activate PKD in order to exit the TGN (5).
FIGURE 2
FIGURE 2
Golgi proteins roles in tumor dissemination and invasion. Golgi proteins are involved in multiple processes linked to tumor aggressiveness, such as the secretion of MMPs, cell migration and regulation of apico-basal polarity, and their roles have been assessed in different tumors. This picture summarizes the different Golgi signaling proteins involved in regulating specific MMPs secretion, the Golgi-localized proteins that are part of the CDC-42 complex for directed cell migration, and finally the PKD signaling pathway that promotes the maintenance of apico-basal polarity.
See this image and copyright information in PMC

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