SEPT9_i1 and Septin Dynamics in Oncogenesis and Cancer Treatment
Abstract
:1. Introduction
2. Septin 9 and SEPT9_i1—Structure as Basis of Protein Interactions
3. SEPT9_i1 Contributes to Cancer Formation, Malignancy, and Resistance to Treatment
3.1. SEPT9_i1 Prevents Degradation, Facilitates Transport and Scaffolds for Transcription Factors
3.2. SEPT9_i1 Is Crucial for Integrating Septin Dynamics with Other Components of the Cytoskeleton
3.2.1. SEPT9_i1 Is a Crucial Factor in Cell Invasiveness
3.2.2. SEPT9_i1 Interaction with Microtubules Contributes to Taxane Resistance
3.3. Competition and Synergism between SEPT9_i1 and Its Isoforms and Their Relevance to Cancer Biology
4. SEPT9_i1 and Other Septins as Novel Therapeutic Targets in Cancer
4.1. Forchlorfenuron—Mechanism and Effects of Action
4.2. Septin Chemotherapy beyond Cytotoxicity
4.2.1. Septin Inhibition as a Tool for Overriding Tumor Resistance to Other Forms of Treatment
4.2.2. Septin Inhibitors as Potential Migrastatics
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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SEPT9_i1-Associated Protein | Mechanism of Interaction | Source |
---|---|---|
JNK, HIF-1 α | SEPT9_i1 increases HIF-1 α and JNK’s activity by preventing their degradation and, in the case of HIF-1 α, enhancing unclear shuttling [59,127]. | HIF-1 α and JNK have both been implicated in the development of taxane resistance [68]. |
MAP4 | SEPT9_i1 competes for the same binding spot on the microtubules with MAP4 [99]. | MAP4 halts tubulin depolymerization—its inhibition counteracts the microtubule-stabilizing effect of taxanes [92]. |
TTL, TTLL5, TTLL11, CCP1, CLIP-170, MCAK | SEPT9_i1 scaffolds for TTLL5, TTLL11, and CCP1, which regulate tubulin polyglutamylation, increasing the recruitment of CLIP-170 and MCAK [93,98]. | CLIP-170 and MCAK are crucial for maintaining microtubule dynamic instability—the state associated with resistance to MTAs [96,97]. |
- | SEPT9_i1 overexpression induces EMT in tumor cells in vitro—the exact mechanism and associated proteins remain unknown [101]. | EMT is a process strongly implicated in tumor resistance to various forms of treatment, including taxane therapy [128]. |
SEPT9_i1-Associated Protein | Mechanism of Interaction | Source |
---|---|---|
ARHGAP4 | SEPT9 and SEPT2 suppress ARHGAP4, which increases promigratory protein Rho activity [89]. | RhoA/ROCK pathway is crucial to various cellular processes involved in tumor cell motility and its ability to metastasize, including stress fiber stabilization and the formation of FAs [134]. |
RhoA, ROCK | SEPT9_i1 increases activation of RhoA/ROCK pathway, leading to increased stress fiber formation and stability [27]. | |
FAK, Src, Paxilin | FA maturation is amplified through increased recruitment of FAK, Src, and paxillin facilitated by SEPT9_i1 [27]. | Focal adhesions are involved in the formation of invadopodia, dissolution of ECM, and other processes involved in metastases [135]. |
JNK, HIF-1 α | JNK and HIF-1 alpha, known for their promigratory properties, are protected from degradation by SEPT9_i1 [59,127]. | HIF-1 and JNK are known for their promigratory influence, with HIF-1 even being named the “master regulator of metastasis” [71,78]. |
Cortactin, TKS5 | SEPT9_i1 recruits cortactin and TKS5 during the formation of juxtanuclear invadopodia. The exact mechanism remains unclear—stabilization of the nuclear envelope has been proposed as a contributor [88]. | Invadopodia are some of the most important structures involved in tumor cell invasion and metastases [86]. |
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Jędrzejczak, P.; Saramowicz, K.; Kuś, J.; Barczuk, J.; Rozpędek-Kamińska, W.; Siwecka, N.; Galita, G.; Wiese, W.; Majsterek, I. SEPT9_i1 and Septin Dynamics in Oncogenesis and Cancer Treatment. Biomolecules 2024, 14, 1194. https://doi.org/10.3390/biom14091194
Jędrzejczak P, Saramowicz K, Kuś J, Barczuk J, Rozpędek-Kamińska W, Siwecka N, Galita G, Wiese W, Majsterek I. SEPT9_i1 and Septin Dynamics in Oncogenesis and Cancer Treatment. Biomolecules. 2024; 14(9):1194. https://doi.org/10.3390/biom14091194
Chicago/Turabian StyleJędrzejczak, Piotr, Kamil Saramowicz, Justyna Kuś, Julia Barczuk, Wioletta Rozpędek-Kamińska, Natalia Siwecka, Grzegorz Galita, Wojciech Wiese, and Ireneusz Majsterek. 2024. "SEPT9_i1 and Septin Dynamics in Oncogenesis and Cancer Treatment" Biomolecules 14, no. 9: 1194. https://doi.org/10.3390/biom14091194