Mechanisms of activation and key roles of SGK3 under physiological conditions and in prostate and breast cancer.

: The serum and glucocorticoid inducible protein kinase (SGK) family signals downstream of phosphoinositide-3-kinase (PI3K) and is made up of three isoforms: SGK1, 2, and 3. respectively, and their activity is dependent on growth factor activation. Among these SGK family one such potential target and less explored enzyme is SGK3. SGK3 regulate a range of basic cellular processes, such as cell proliferation, migration and survival. Thus play an important role in cancer development. These kinase-signaling pathways present both opportunities and challenges for cancer therapy. In this paper, we reviewed the status of SGK3 regulation and its role in normal cell physiology and transformation. In addition, the potential roles of SGK3 signal transduction in breast cancer and prostate cancer are discussed.

Download Full-text

Signalling specificity in the Akt pathway in breast cancer

Biochemical Society Transactions ◽

10.1042/bst20140160 ◽

2014 ◽

Vol 42 (5) ◽

pp. 1349-1355 ◽

Cited By ~ 48

Author(s):

Abbe R. Clark ◽

Alex Toker

Keyword(s):

Breast Cancer ◽

Protein Kinase ◽

Akt Pathway ◽

Cellular Processes ◽

Akt Isoforms ◽

Isoform Specificity ◽

Novel Targets ◽

Phosphoinositide 3 Kinase ◽

Protein Kinase Akt ◽

Signalling Cascade

Aberrant activation of fundamental cellular processes, such as proliferation, migration and survival, underlies the development of numerous human pathophysiologies, including cancer. One of the most frequently hyperactivated pathways in cancer is the phosphoinositide 3-kinase (PI3K)/Akt signalling cascade. Three isoforms of the serine/threonine protein kinase Akt (Akt1, Akt2 and Akt3) function to regulate cell survival, growth, proliferation and metabolism. Strikingly, non-redundant and even opposing functions of Akt isoforms in the regulation of phenotypes associated with malignancy in humans have been described. However, the mechanisms by which Akt isoform-specificity is conferred are largely unknown. In the present review, we highlight recent findings that have contributed to our understanding of the complexity of Akt isoform-specific signalling and discussed potential mechanisms by which this isoform-specificity is conferred. An understanding of the mechanisms of Akt isoform-specificity has important implications for the development of isoform-specific Akt inhibitors and will be critical to finding novel targets to treat disease.

Download Full-text

RAB11-Mediated Trafficking and Human Cancers: An Updated Review

Biology ◽

10.3390/biology10010026 ◽

2021 ◽

Vol 10 (1) ◽

pp. 26

Author(s):

Elsi Ferro ◽

Carla Bosia ◽

Carlo C. Campa

Keyword(s):

Plasma Membrane ◽

Normal Cell ◽

Vesicular Trafficking ◽

Small Gtpase ◽

Cell Physiology ◽

Biological Mechanisms ◽

Cellular Processes ◽

Human Cancers ◽

Toxic Materials ◽

Dependent Pathway

Many disorders block and subvert basic cellular processes in order to boost their progression. One protein family that is prone to be altered in human cancers is the small GTPase RAB11 family, the master regulator of vesicular trafficking. RAB11 isoforms function as membrane organizers connecting the transport of cargoes towards the plasma membrane with the assembly of autophagic precursors and the generation of cellular protrusions. These processes dramatically impact normal cell physiology and their alteration significantly affects the survival, progression and metastatization as well as the accumulation of toxic materials of cancer cells. In this review, we discuss biological mechanisms ensuring cargo recognition and sorting through a RAB11-dependent pathway, a prerequisite to understand the effect of RAB11 alterations in human cancers.

Download Full-text

ARe we there yet? Understanding androgen receptor signaling in breast cancer

npj Breast Cancer ◽

10.1038/s41523-020-00190-9 ◽

2020 ◽

Vol 6 (1) ◽

Author(s):

Anna R. Michmerhuizen ◽

Daniel E. Spratt ◽

Lori J. Pierce ◽

Corey W. Speers

Keyword(s):

Breast Cancer ◽

Prostate Cancer ◽

Androgen Receptor ◽

Breast Cancers ◽

Androgen Receptor Signaling ◽

Cellular Processes ◽

Treatment And Prevention ◽

Cancer Types ◽

Prevention Of Cancer

Abstract The role of androgen receptor (AR) activation and expression is well understood in prostate cancer. In breast cancer, expression and activation of AR is increasingly recognized for its role in cancer development and its importance in promoting cell growth in the presence or absence of estrogen. As both prostate and breast cancers often share a reliance on nuclear hormone signaling, there is increasing appreciation of the overlap between activated cellular pathways in these cancers in response to androgen signaling. Targeting of the androgen receptor as a monotherapy or in combination with other conventional therapies has proven to be an effective clinical strategy for the treatment of patients with prostate cancer, and these therapeutic strategies are increasingly being investigated in breast cancer. This overlap suggests that targeting androgens and AR signaling in other cancer types may also be effective. This manuscript will review the role of AR in various cellular processes that promote tumorigenesis and metastasis, first in prostate cancer and then in breast cancer, as well as discuss ongoing efforts to target AR for the more effective treatment and prevention of cancer, especially breast cancer.

Download Full-text