PDK1: A signaling hub for cell migration and tumor invasion

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• 作者：Paolo Armando Gagliardi^a ; ^b ; Laura di Blasio^a ; ^b ; Luca Primo^a ; ^b ; ^c ; ^{luca.primo@unito.it" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Akt ; v-Akt murine thymoma viral oncogene homolog product ; CDC42 ; cell division cycle 42 ; DGKs ; diacylglycerol kinases ; ECM ; extracellular matrix ; EGF ; Epidermal Growth Factor ; FA ; focal adhesions ; GSK3 ; glycogen synthase kinase 3 ; HM ; hydrophobic motif ; Ins3P ; inositol 1 ; 4 ; 5-trisphosphate ; Ins3PR ; Ins3P receptor ; MLC2 ; myosin regulatory light chain 2 ; MMP-2 ; matrix metalloproteinase-2 ; MyPT1 ; myosin phosphatase target subunit 1 ; PAK1 ; p21-activated kinase 1 ; PDGF ; platelet-derived growth factor
• 刊名：Biochimica et Biophysica Acta (BBA)-Reviews on Cancer
• 出版年：2015
• 出版时间：December 2015
• 年：2015
• 卷：1856
• 期：2
• 页码：178-188
• 全文大小：1805 K

文摘

The ability of cells to migrate is essential for different physiological processes including embryonic development, angiogenesis, tissue repair and immune response. In the context of cancer such abilities acquire dramatic implications, as they are exploited by tumor cells to invade neighboring or distant healthy tissues.

3-Phosphoinositide dependent protein kinase-1 (PDK1 or PDPK1) is an ancient serine-threonine kinase belonging to AGC kinase family. An increasing amount of data points at a pivotal role for PDK1 in the regulation of cell migration. PDK1 is a transducer of PI3K signaling and activates multiple downstream effectors, thereby representing an essential hub coordinating signals coming from extracellular cues to the cytoskeletal machinery, the final executor of cell movement. Akt, PAK1, β3 integrin, ROCK1, MRCKα and PLCγ1 are, according to the literature, the signaling transducers through which PDK1 regulates cell migration.

In addition, PDK1 contributes to tumor cell invasion by regulating invadopodia formation and both amoeboid and collective cancer cell invasion. This and other pieces of evidence, such as its reported overexpression across several tumor types, corroborate a PDK1 role tumor aggressiveness.

Altogether, these findings indicate the possibility to rationally target PDK1 in human tumors in order to counteract cancer cell dissemination in the organism.