The Role of Src-Phosphorylation at the α1-Na/K-ATPase at Caveola in the Pathogenesis and Treatment of NASH Related Hepatocellular Carcinoma: Overview of Published Literature

Udoh U1-2, Sanabria JD1-2, Smith G1-2, Schade M1-2, Sanabria JA1-2, Mallick A1-2, Rajan PK1-2, Beltran N1-2, Banerjee M1-2, Udoh G1-2, Sodhi K1-2, Pierre S2, Xie Z2£, Shapiro J1-2 and Sanabria J1-3*

1Marshall Institute for Interdisciplinary Research, Marshall University Joan Edwards School of Medicine, USA
2Department of Surgery, Marshall Institute for Interdisciplinary Research, USA
3Department of Surgery, Nutrition and Metabolomic Core Facility, Case Western Reserve University School of
Medicine, USA
£In memory of a scientist and mentor

^*Correspondance to: Juan Sanabria 

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Abstract:

The incidence of Hepatocellular Carcinoma (HCC) and its related mortality is increasing, becoming
the 2nd and fastest-growing cause of cancer related mortality worldwide. In particular, the rise of HCC
can be attributed to the cellular metabolic disturbances promoted by the epidemic of obesity and
the lack of markers for its early detection. With few treatment options and a 50% to 70% recurrence
rate after resection or loco-regional treatment, HCC has become a major and steadily increasing
global health challenge. This review focuses on the current knowledge related to the pathogenesis
of NASH-related HCC in order to provide a novel pathway for theoretical treatment options. For
instance, regulation of Src-phosphorylation by the α1-subunit of the Na/K-ATPase may initiate
protein interactions, beginning at the anchoring-Caveolin-1 in the plasma membrane, that promote
disturbances in the intrinsic apoptotic pathway. This apoptotic cascade is activated and regulated by
the mitochondria during energy distress, as often observed in NASH-related HCC. As part of this
pathway, the Smac/DIABLO-survivin signaling equilibrium may play a pivotal role in regulating the
pathogenic ‘apoptotic switch’ in NASH related malignancy. Additionally, we propose inhibition of
Src phosphorylation at the α1-Na/K-ATPase as a putative target for the treatment of HCC.

Keywords:

Hepatocellular carcinoma; NASH, Na/K-ATPase-α1-Caveolin-1; Survivin; Smac/ DIABLO; Hedgehog; Apoptosis

Cite the Article:

Udoh U, Sanabria JD, Smith G, Schade M, Sanabria JA, Mallick A, et al. The Role of Src-Phosphorylation at the α1- Na/K-ATPase at Caveola in the Pathogenesis and Treatment of NASH Related Hepatocellular Carcinoma: Overview of Published Literature. World J Surg Surgical Res. 2020; 3: 1232..