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The microtubule-affinity regulating kinases (MARKs) family plays a crucial role in regulating breast cancer development and progression. However, its precise function and the relevant molecular mechanism in breast cancer have not yet been elucidated. In this study, analysis of The Cancer Genome Atlas (TCGA) data revealed that MARK2 expression was markedly upregulated in breast cancer tissues, and high expression of MARK2 was correlated with poor survival. Functional assays showed that MARK2 deletion or inhibition suppressed aerobic glycolysis and cell growth as well as induced cell cycle arrest and apoptosis in breast cancer cells. Mechanistically, MARK2 stimulates mTOR-mediated hypoxia-inducible factor 1 alpha (HIF-1α) transcription activity and represses p53-transcription activity in breast cancer cells. TCGA data revealed that MARK2 expression was positively correlated with mTOR, Raptor, S6K1, glucose transporter 1, lactate dehydrogenase, HIF-1α, and 4E-BP1 expression, whereas negatively correlated with p53, p21, and Bax in breast cancer tissue. Conclusively, our study demonstrated that MARK2 promotes breast cancer aerobic glycolysis and cell proliferation, and inhibits apoptosis, in part, through regulating mTOR/HIF-1α and p53 signaling pathways. Overall, these findings point to the potential of targeting MARK2 for breast cancer treatment., (© 2022 Wiley Periodicals LLC.)

The Salt-inducible kinase (SIKs) belongs to an AMPK-related family kinase, an isoform of the SIK family, SIK1 gets frequently downregulated in various types of cancer contribute to tumorigenesis. However, its precise role in breast cancer and the relevant molecular mechanism remains unclear. Herein, analysis of the clinical data reveals that SIK1 expression was significantly downregulated in breast cancer tissues, and closely associated with poor survival rate in breast cancer. SIK1 is functionally stimulating oxidative phosphorylation, which in turn inhibits aerobic glycolysis and cell proliferation in breast cancer cells. Mechanistically, SIK1 directly interacted with p53 and positively regulates its transcriptional activity, thereby facilitates oxidative phosphorylation in breast cancer cells. The knockdown of SIK1 downregulates p53 transcriptional activity, leading to stimulation of aerobic glycolysis and cell proliferation. Moreover, high expression of SIK3 stimulates mTOR-mediated aerobic glycolysis and cell proliferation of breast cancer cells. These findings suggest that SIK isoforms plays distinct role in aerobic glycolysis and cell growth of breast cancer, attenuated SIK1/p53 signaling suppresses oxidative phosphorylation and growth inhibitory effect in breast cancer cells, while enhanced SIK3/mTOR signaling potentiates aerobic glycolysis mediated cell growth in breast cancer cells., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Salt-inducible kinases 3 (SIK3) belong to the AMPK-related family of kinases, which have been implicated in the regulation of cell metabolism, cell polarity remodelling, and epithelial-mesenchymal transition. Elevated SIK3 expressions in breast cancer cells are shown to contribute to tumorigenesis; however, the underlying mechanism remains to be elucidated. In this study, we demonstrate that SIK3 expression is upregulated and concurrently high expression of SIK3 is associated with poor survival in breast cancer. Specifically, SIK3 knockdown revealed that SIK3 is required for the mTOR/Akt signaling pathway and proliferation of breast cancer cells. Furthermore, our findings showed that Emodin (EMO) combined with Berberine (BBR) significantly inhibited SIK3 activity, leading to reduced cell growth, increased cell cycle arrest and apoptosis in breast cancer cells, but not in non-malignant breast epithelial cell line. Mechanistic studies further reveal that EMO and BBR in combined treatment inhibited SIK3-potentiated mTOR-mediated aerobic glycolysis and cell growth in breast cancer cells. Moreover, combination treatments attenuate Akt signaling, thereby inducing G0/G1 phase cell cycle arrest and apoptosis of breast cancer cells in a SIK3-dependent manner. CRISPR/Cas9 or siRNA-mediated SIK3 knockout/knockdown showed an opposite trend in both the luminal and basal-like breast cancer. Collectively, our findings reveal that combination of EMO and BBR attenuates SIK3-driven tumor growth in breast cancer, and thus, EMO and BBR might be a novel SIK3 inhibitor explored into the prevention of breast cancer., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Breast cancer is the most ubiquitous type of neoplasms among women worldwide. Molecular aberrations associated with breast development and progressions have been extensively investigated in recent years. An AMP-activated kinase (AMPK) initially identified as a cellular energy sensor that plays a crucial role in cellular energy homeostasis. Intensive research over the last decade about the molecular mechanisms of AMPK has demonstrated that AMPK mediated diverse biological functions are achieved through phosphorylation and regulation of multiple downstream signaling molecules in normal tissue. Downregulation of AMPK activity or decreased level involved in the promotion of breast tumorigenesis, and thus activation of AMPK found to oppose tumor progression. In this review, we epitomize the recent advances in exploring the tumor suppressor function of AMPK pathways. Besides, we discuss the developments in the area of AMPK activator and its molecular mechanisms for breast cancer treatment., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

We are developing optical methods based on near infrared Raman spectroscopy and fluorescence photon migration for diagnosis and localization of breast cancer. We demonstrate the ability of Raman spectroscopy to classify accurately normal, benign and malignant breast tissues, an important step in developing Raman spectroscopic needle probes as a tool for improving the accuracy of needle biopsy. We also show that photon migration imaging can be used to localize accurately small fluorescent objects imbedded in a thick turbid medium with realistic optical properties, thus demonstrating the potential of this technique for optical imaging.