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Review
. 2021 Oct 28:9:690306.
doi: 10.3389/fcell.2021.690306. eCollection 2021.

Targeting Phosphatases and Kinases: How to Checkmate Cancer

Alice Turdo  1 , Caterina D'Accardo  1 , Antonino Glaviano  2 , Gaetana Porcelli  1 , Cristina Colarossi  3 , Lorenzo Colarossi  3 , Marzia Mare  3 , Naida Faldetta  4 , Chiara Modica  2 , Giuseppe Pistone  1 , Maria Rita Bongiorno  1 , Matilde Todaro  1   5 , Giorgio Stassi  2
Affiliations
Review

Targeting Phosphatases and Kinases: How to Checkmate Cancer

Alice Turdo et al. Front Cell Dev Biol. .

Abstract

Metastatic disease represents the major cause of death in oncologic patients worldwide. Accumulating evidence have highlighted the relevance of a small population of cancer cells, named cancer stem cells (CSCs), in the resistance to therapies, as well as cancer recurrence and metastasis. Standard anti-cancer treatments are not always conclusively curative, posing an urgent need to discover new targets for an effective therapy. Kinases and phosphatases are implicated in many cellular processes, such as proliferation, differentiation and oncogenic transformation. These proteins are crucial regulators of intracellular signaling pathways mediating multiple cellular activities. Therefore, alterations in kinases and phosphatases functionality is a hallmark of cancer. Notwithstanding the role of kinases and phosphatases in cancer has been widely investigated, their aberrant activation in the compartment of CSCs is nowadays being explored as new potential Achille's heel to strike. Here, we provide a comprehensive overview of the major protein kinases and phosphatases pathways by which CSCs can evade normal physiological constraints on survival, growth, and invasion. Moreover, we discuss the potential of inhibitors of these proteins in counteracting CSCs expansion during cancer development and progression.

Keywords: cancer stem cell; kinase; phosphatase; phosphatase and kinase inhibitors; targeted therapies.

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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.

Figures

FIGURE 1
FIGURE 1
Landscape of the most common kinases and phosphatases network in cancer stem cells. Kinase activating phosphorylation is shown with arrowed lines, inhibitory phosphorylation or non-phosphorylation is indicated with blocked lines, and dephosphorylation, exerted by phosphatases (black squares), is displayed with round-ended lines. Dotted lines represent indirect effect. TFs1: Transcription Factors (Jun, ATF2, RNPK, p53, NFAT4, Shc); TFs2: Transcription Factors (CHOP, ATF2, MNK, MSK, MEF2, Elk-1); TFs3: Transcription Factors (Elk-1, Ets-2, RSK, MNK, MSK, cPLA2).
FIGURE 2
FIGURE 2
Timeline of FDA approvals for kinase inhibitors.
See this image and copyright information in PMC

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